Helper T cells producing IL-17 (Th17) have high plasticity: restimulation of lymphocytes in an inflammatory environment can induce their transformation into cells with another phenotype, and a shift towards Th1 is the most common. The result of this transformation is the appearance of cells expressing along with the classical markers of Th17 cells key Th1-associated molecules. In its most general form, this population is represented by CD4⁺CD161⁺CCR6⁺CXCR3⁺IL-17⁺IFNγ⁺Т cells, and in the current literature it is most often referred to as Th17.1. Some Th17.1 cells can completely lose the production of IL-17, while maintaining the expression of other Th17-associated molecules; these are the so-called ex-Th17 cells (CD4⁺CD161⁺CCR6⁺CXCR3⁺IL-17^- IFNγ⁺Т cells). Consequently, the population of Th1-polarized Th17 includes Th17.1, ex-Th17 cells and a number of additional transitional forms. It has unique functional properties – an increased pro-inflammatory potential and the ability to overcome histohematic barriers. It is these cells that are currently assigned a key role in the pathogenesis of many autoimmune diseases, and the process of Th17 redifferentiation into Th1 is considered as a promising therapeutic target. However, the development of this direction is complicated by the weak comparability of data on the size of such a population. The analysis of methods for determining Th1-polarized Th17 in vivo and in vitro, carried out in this work, made it possible to resolve these contradictions and develop optimal approaches to identifying this population. In most studies, especially clinical ones, it is identified by co-expression of key cytokines (IL-17/IFNγ) or chemokine receptors (CCR6/CXCR3), rarely by their combination. In this approach, co-expression of CCR6/ CXCR3 marks the total population of Th1-like Th17, including both Th17.1 and ex-Th17, while co-expression of IL-17/IFNγ cytokines identifies only Th17.1 cells, and the subpopulation of ex-Th17 is misclassified as classic Th1 in this case. Such “underestimation” of the ex-Th17 subpopulation significantly marks down the results, since it is ex-Th17 that accounts for the bulk of Th1-like Th17. And only a simultaneous assessment of the co-expression of cytokines and Th17-associated membrane molecules allows identification Th17.1 and exTh17 cells separately, which is important to consider when interpreting data on the problem and when planning clinical trials.

Numerous studies show the role of the cytokine network in the pathogenesis of anxiety and depression. However, at present, studies of the correlation between the levels of pro-inflammatory and antiinflammatory cytokines and the level of emotional stress are rather few. The aim of the study was to analyze the serum levels of pro-inflammatory and anti-inflammatory cytokines and the emotional state in apparently healthy women depending on age. Serum levels were tested IL-1β, IL-6, IL-17, IFNγ, IL-10 and IL-4 in 100 apparently healthy women, who were divided into 3 groups depending on age (WHO): 18-44 (young age) 30 people, 45-59 (middle age) 40 people, 60-74 (old age) 30 people (sandwich variant of enzyme-linked immunosorbent assay, pg/mL). To assess the emotional component of health, all the subjects passed the questionnaire SF-36 “Assessment of the quality of life”. Statistical processing of the obtained data was carried out using the analytical software IBM SPSS Statistics, 22.0. In practically healthy women, an increase in the values of IL-1β and IL-6 was found in the elderly group (p < 0.05), while no differences were found between the groups of young and middle age. The level of IFNγ in all age groups of women did not differ significantly. At the same time, in the elderly group, the levels of IFNγ in 40% ranged from 1.04 to 8.76 pg/mL, and in 60% of women – from 24.85 to 28.5 pg/mL. IL-17 was also high (p < 0.05-0.01) in the group of women aged 60-74. In the anti-inflammatory link, the opposite picture was observed, for example, in young and middle-aged women, the levels of IL-10 and IL-4 were higher than in the elderly group. Thus, the analysis made it possible to state that the parameters of the cytokine profile and emotional state in women are associated with age.

T lymphocytes of the 2^nd type of immune response contribute to the development and exacerbation of inflammation, mainly allergic. Increased inflammation with prolonged exposure to adverse factors during the work of firefighters can lead to the development of various diseases. Evaluation of the immunity of firefighters is important for the appointment of adequate treatment and prevention of infectious and allergic diseases. This paper aimed to analyze the indicators of immunity in employees of the state fire service of EMERCOM of Russia, depending on the age and intensity of the professional workload. The surveyed were men (n = 79), mean age 31 years, work experience from 1 to 22 years, with different workload intensity. In peripheral blood, flow cytometry (Navios, FC 500, Beckman Coulter) was used to evaluate subpopulations of monocytes, the relative number of T lymphocytes of the 2^nd type of immune response CD3⁺CD294⁺. The concentration of total immunoglobulin E (Immulite) was determined. From nasal secretions, the content of secretory immunoglobulin A (Vector Best) was evaluated (n = 30). Statistical processing of the results was performed using the Statistica 12.0 package (StatSoft). An increase in the number of CD3⁺CD294⁺ cells was observed in 16.5%. A direct correlation was found between the number of T lymphocytes 2 and the age of the examined persons (р < 0.05). In the group of firefighters with a more intense workload, an increase in the number of CD3⁺CD294⁺ cells were 5 times higher (р < 0.05). Among patients who had any disease of the respiratory tract, an increase in this population was observed statistically significantly more often – in 26% of cases versus 11.5%. A strong direct correlation was found between the number of T lymphocytes 2 and the duration of smoking experience (р < 0.05). A direct correlation was established between the number of T lymphocytes 2 and the concentration of total IgE (р < 0.05). A decrease in secretory IgA in the secret from the nasal passages was observed in 23% of firefighters, in 13% of the examined, the indicator went beyond the upper limit of the reference interval. Significantly more often revealed the deviation of this indicator from the reference values in firefighters with a high workload. An increase in the subpopulation of classical monocytes was established in the group of those examined with a high number of CD3⁺CD294⁺ cells (p < 0.05). Thus, with an increase in the professional workload of firefighters in unfavorable conditions of service, inhibition of protection to infection and aggravation of damage to the respiratory tract with an increase in the 2^nd type of immune response are noted. Evaluation of the number of type 2 T lymphocytes in peripheral blood will reveal a predisposition to the T2 profile of immune inflammation, which will contribute to a personalized approach to patient management.

Chronic psycho-emotional stress can cause dysfunction of neuroimmunoendocrine dysregulation with consequences in the form of a violation of the functional potential of the immune system. Adaptation to new living conditions at the start of studies at a medical university is one of the inevitable circumstances that first-year students overcome. Education under the military training program at a medical university carries an additional stress load in this aspect. Research on the mechanisms of formation of adaptive reactions of the immune system during training under the military training program for officers of the medical service is of undoubted interest. The purpose of the study was to compare the clinical manifestations of immune-mediated pathology and the parameters of adaptive and innate immunity of medical students depending on the length of service and training program. Under observation were 104 medical students, all men, of which 37 were first-year students and 67 were third-year students of a medical university. The subjects of each course were divided into two subgroups depending on the training program. The group of first-year students consisted of 18 people from the military training center (VTC) and 19 people from the medical and preventive faculty (LPF). Among the third-year students of the VUC – 31, LPF – 36. For the clinical characterization of the incidence during the year of study, registration cards for the analysis of immune-mediated pathology were used, the parameters of the immune system at the end of the spring semester were studied using standard methodological approaches. The data obtained indicate that in the first year students with an additional load in the form of a military training program have a more difficult time adapting to learning in comparison with first-year students of the medical faculty. These differences consist in a more frequent and significant clinical manifestation of infectious pathology and are reflected in the functional potential of cellular parameters of innate immunity. The statement of signs of inhibition of the functional potencies of macrophage cells and natural killers in firstyear students of a military training center is an alarming factor in the possible disruption of the adaptive reserves of the immune response system, which probably suggests the need to develop programs to prevent the negative impact of stress-forming factors. By the third year of study, the students of the military training center have the best clinical and immunological indicators of the functioning of the immune system in comparison with the students of the standard educational program of general practitioners. It is likely that during this period the process of psychological adaptation of military medical students is completed.

Causing millions of cases worldwide every year, influenza is one of the most common respiratory infections. The effectiveness of influenza vaccination and the nature of the resulting immune response may vary depending on the vaccine composition and age group. Since children are at the highest risk of disease and act as the main carriers of influenza, the assessment of the immunological efficacy of vaccines in this group is crucial for controlling the epidemic. Therefore, this study aimed to evaluate the characteristics of the humoral immune response in children after immunization with various types of inactivated influenza vaccines.
An observational study was conducted in the 2019-2020 season and involved 230 children (< 18 years old) and a comparison group of 87 adults aged 18 to 60 years. The subjects, who provided informed consent to participate, were vaccinated with one of three vaccines (Grippol Plus, Sovigripp, or Ultrix) in an open-label fashion. The humoral immune response was assessed by measuring the hemagglutination inhibition (HI) titer in the paired sera taken before and three weeks after vaccination.
The immunogenicity of the vaccines in the age group under 18, met the CPMP criteria for the assessment of inactivated influenza vaccines in terms of the fold increase in antibody titers and the proportion of individuals with seroconversion to all three components (A/H1N1pdm09, A/H3N2, and B/Victoria). Although 6 to 18-year-old participants showed a more robust immune response to the B/Victoria component compared to the adult participants (aged 18 to 60), it was insufficient to ensure that 70% of the participants have a protective antibody titer.
A comparative analysis of the vaccines’ immunogenicity was carried out for a subgroup of children aged 6-18 who had initially low antibody levels at the time of vaccination. The analysis showed that the split vaccine Ultrix outperformed the adjuvanted vaccine Grippol Plus in generating an antibody response to the component B/Victoria; however, the antibody responses to the A/H1N1pdm09 and A/H3N2 components did not differ between the two vaccines. The children under 6 years of age demonstrated a less pronounced humoral immune response to vaccination compared with the other age groups, which may be due to the age-related characteristics of the immune system in children of preschool age.

The ongoing coronavirus disease (COVID-19) pandemic over the past three years has caused close attention to the problem of herd immunity, which is understood as: "resistance to the spread of a contagious disease within a population or herd". Collective immunity is formed both as a result of infection (natural spread of the pathogen in a population of susceptible individuals) and as a result of the use of specific vaccines. During the COVID-19 pandemic, both mechanisms for the formation of collective immunity were realized. In the first wave, there was a natural formation of collective immunity to the virus following recoveries from COVID-19 caused by pandemic spread of SARS-CoV-2. Starting from December 2020, the widespread use of specific vaccines against SARS-CoV-2 began in the USA, Great Britain, China, Russia, and a number of other countries. This launched the process of post-vaccination collective immunity formation; its features have depended on the vaccine types implemented. Currently, in those countries where vaccination and revaccination of recovered patients is widely carried out, immunity is "hybrid" in nature.
Several commonalities should be noted in the pandemic experience: a somewhat regular, periodic (wavelike) nature of the COVID-19 epidemic process; changes in pathogen genetics in variants in all countries; and expansive mass vaccination programs in many populations. From these, we can draw some conclusions about the general trend for all countries in the formation of collective immunity during the pandemic:
At the beginning of the pandemic in 2020, overall population seroprevalence did not exceed 20%. Other findings were: the highest seroprevalence rates were noted in the children's age group; pronounced regional differences were revealed; and the highest indicators were noted among medical workers. Collective immunity developed as a result of infection or illness, and in the majority of seropositive volunteers, it was represented by antibodies to both antigens.
At the height of the pandemic in the summer of 2021, population seroprevalence reached 50%. This was due to both a significant number of convalescents and the start of mass vaccination campaigns. In all countries, specific differences in seroprevalence (by age, region, profession) leveled out, leading to more uniformity. During this period, the formation of "hybrid" immunity is clearly prominent, and the proportion of individuals with antibodies to RBD alone increased (due to vaccination with vector vaccines).  
Later, mass vaccination, as well as involvement of most of the population in the epidemic process due to the emergence of the highly contagious Omicron strain, raised the level of collective immunity to 80-90%. This led to a sharp decrease in COVID-19 incidence in the second half of 2022 in all countries participating in the study. In the later stages of the pandemic (2022-2023), almost 90% of seropositive volunteers had hybrid immunity, reflected as antibodies to both antigens (Nc, RBD).

The article is devoted to the development of a cytokine diagnostic method for predicting the development of critical conditions in newborns born to mothers with COVID-19, which is of great importance for health authorities when organizing specialized neonatology and pediatric services.
Objective: to develop a method of noninvasive cytokine diagnostics for predicting the development of critical conditions in newborns born from a mother with COVID-19.
The proposed method allows early diagnosis and prevention of the development of critical conditions in newborns, which is of great practical importance. The control of urine cytokines in dynamics determines the prognosis of the development of critical conditions, both in the early and late period of adaptation of newborns. As a marker of the inflammatory process and a key cytokine of bone resorption, IL-17A plays a complex role in the adaptation process of newborns born from a mother with COVID-19. Newborns born from a mother with COVID-19 have an increase in IFNγ and IFNα in the blood on the first day of life against the background of an increase in IL-17A by 1.48 times, which shows the risk of developing both infection and osteogenesis disorders. Activation of interferon status by the 7th day of life in newborns was established against the background of an increase in the key cytokine of bone resorption (IL-17A). A decrease in the urine of molecular markers of vascular endothelial damage – MSR-1 by 4.25 times was found in newborn children born from a mother infected with COVID-19. A decrease in VEGF in the urine of newborns was found, both with COVID-19 infection in the mother and in its absence. Non-invasive urine cytokine diagnostics allows achieving economic efficiency by reducing hospital beds, as well as medical efficiency due to minimal traumatization of newborns.

In this article, we explore the role of macrophage-derived chemokine (MDC/CCL22) in COVID-19 immunity. The study included plasma samples of 289 patients with PCR-verified COVID-19 from specialized hospitals. The blood samples were collected at admission, approximately 7 days after the start of infection. Genetic testing of the virus was performed in nasopharyngeal swabs to determine the viral strain for each patient. We also included blood plasma of 69 convalescent patients who had recovered from COVID-19 more than a month prior to the study. Additionally, 51 healthy donors were included in the study as controls.
The concentrations of MDC/CCL22 and other cytokines and chemokines were measured with multiplex analysis using Luminex MagPix Technology. The results showed that COVID-19 patients had significantly lower MDC levels in their plasma, regardless of the SARS-CoV-2 strain, compared to healthy donors. This finding suggests that MDC/CCL22 depletion may play a role in COVID-19 immunity. Furthermore, convalescent patients still showed decreased concentrations of MDC/CCL22 more than a month after infection, indicating that this depletion may persist even after recovery.
We propose two mechanisms that can explain the reasons leading to MDC/CCL22 depletion. The first is binding and inactivation of this chemokine with SARS-CoV-2 peptides, making it not only undetectable for commercial kits, but also less functionally active. Another mechanism is the dysfunction of its effector cells (e.g., DCs and macrophages). Lymphopenia following COVID-19 can potentially be explained by the absence of MDC/CCL22. This may lead to a shift towards hyperactivation in the inflammatory response, potentially explaining the severity of COVID-19.
This research sheds light on the importance of MDC/CCL22 in COVID-19 immunity and highlights the need for further investigation into its role in the disease. Understanding the mechanisms behind MDC/CCL22 depletion could provide new insights into the pathogenesis of COVID-19 and inform the development of potential treatments.

SARS-CoV-2 infection is the etiopathogenetic factor of the new coronavirus infection. Susceptibility to the virus and, accordingly, the incidence differs in children and adults. On the one hand, this reflects the age-related features of the immune response. On the other hand, it is realized through the production of a number of cytokines, including IL-2, and reflects the genetically determined features of cytokine production. The aim of the study was to analyze the frequency of occurrence of T-330G polymorphic variants of the IL2 gene in patients with a new coronavirus infection. A total of 145 patients were examined, including 31.0% of children (n = 45) and 69.0% of adults (n = 100). The diagnosis of a new coronavirus infection was verified by RT-PCR confirming the presence of the SARS-CoV-2 virus and identifying clinical symptoms of an upper respiratory tract infection. The control group consisted of 50 healthy volunteer donors. Allele-specific PCR with electrophoretic detection in 3% agarose gel (Litech, Russia) was used to analyze the T-330G polymorphism of the IL2 gene. To compare the frequencies of allele combinations, the χ² test and the odds ratio OR and (95% CI) were used.

The dominant genotype in patients with COVID-19 was the heterozygous GT genotype of the T-330G polymorphism of the IL2 gene. In the group of children at risk of developing a new coronavirus infection, the GG genotype of the T-330G polymorphism of the IL2 gene was associated (31.1% in children and 18.0% in the control group, p < 0.05, OR = 2.047). While the homozygous TT genotype of the T-330G polymorphism of the IL2 gene was a protective genotype (its occurrence rate was 26.7% in patients, 54.0% in the control group, p < 0.05, OR = 0.315). In adults, the heterozygous GT genotype of the T-330G polymorphism of the IL2 gene was associated with the risk of developing a new coronavirus infection (in the group of patients – 44.0% versus control – 28.0%, p = 0.028, OR = 2.020). A low risk of developing the disease was associated with the homozygous TT variant of the T-330G polymorphism of the IL2 gene (in the group of patients 37.0% versus control – 54.0%, p = 0.024, OR = 0.500).

The T-330G polymorphism of the promoter zone of the IL2 gene differently affects its production. The direction of the immune response and its effectiveness depend on the level of IL-2. Understanding the individual factors that determine the features of the immune response can help in understanding the mechanisms of development of COVID-19-associated diseases and the selection of approaches to personalized methods of their treatment.

The 2019 coronavirus disease (COVID-19) pandemic has had an unprecedented impact on health and economies around the world. Direct myocardial injury and cytokine storm, leading to destabilization of preexisting plaques and accelerated formation of new plaques, are two mechanisms that trigger the acute coronary syndrome in COVID-19. There is insufficient data on the immune status of patients with acute coronary syndrome who have undergone COVID-19. The aim of the study was to study T and B cell, humoral immunity depending on the number of cytotoxic T lymphocytes (CD8⁺) in patients with acute coronary syndrome who underwent COVID-19. Materials and methods of research: 65 men with unstable angina pectoris and acute myocardial infarction (acute coronary syndrome) from 40 to 65 years old, who had previously had COVID-19, were examined. A study of peripheral blood was carried out: complete blood count (Medonic device, Sweden), general and specific IgM, IgG, IgA, compliment fragments (Vector Best, Russia). Subpopulations of T and B lymphocytes were determined by flow cytometry. In persons with acute coronary syndrome who underwent COVID-19 with predominantly normal and elevated levels of cytotoxic T cells, a more severe course of the disease was observed: patients with acute myocardial infarction prevailed, they had longer mortality, longer treatment duration, and stent thrombosis was more common. In patients with elevated cytotoxic T cells, there was a maximum increase in erythrocytes, hemoglobin, hematocrit, lymphocytes of both the total number and subpopulations – T helpers, T-NK lymphocytes, NK lymphocytes, T lymphocytes of early and late activation, B1 and B2 lymphocytes, index of NBT-induced test. In patients with normal levels of NK cells, compared with other groups, there was an increase in spontaneous NBT activity and index, a significant decrease in C3a and C5a complement fragments. Prevalence of stent thrombosis and mortality in the group of patients with normal levels of cytotoxic T cells may indicate torpidity of the immune system in these patients with poor outcomes.

This study examines the long-term effects of SARS-CoV-2 infection on immune status. Given the prolonged and profound immune dysregulation observed during acute SARS-CoV-2 infection, it remains to be determined whether these changes translate into subsequent immune system dysfunction in recovering individuals. In this sense, the aim of the study was to study the parameters of the immune system in patients who had undergone SARS-CoV-2 infection.
150 patients who underwent SARS-CoV-2 infection were examined according to 96 parameters using flow cytometry. A complete blood count was performed using a Medonic device (Sweden); ELISA method determined the levels of general and specific IgM, IgG, IgA, compliment fragments (JSC Vector-Best, Russia). The activity of the phagocytes was studied according to the generally accepted method.
The study found that at least four phenotypes of immune system disorders are detected in patients. The first two phenotypes are related to the impairment of innate immune system factors and are associated with a decrease in the number of CD46+ and NK cells. It has been observed that a decrease in CD46+ persists for a long time in a significant number of recovered patients, highlighted by the impaired expression of this marker in various subpopulations of lymphocytes. The decrease in the level of natural killers was accompanied by a compensatory increase in the number of T lymphocytes, mainly due to T helpers and TNK lymphocytes, and the growth of total memory B cells. Two other identified phenotypes are characterized by damage to acquired immune response factors and are associated with damage to B cells and T cytotoxic cells. The relationship of such disorders with damage to hematopoiesis erythrocyte and platelet sprouts, which contribute to the appearance of hypoxia and possible violation of the blood coagulation system, has been shown.
Therefore, the results obtained indicate a long-term pronounced damage to the immune system in postCOVID patients that requires immunocorrection of these disorders.

The pandemic of the new COVID-19 coronavirus infection has created a public health emergency in the Russian Federation in 2020-2022. COVID-19 causes various consequences, often manifested by the endocrine system dysfunction. The rationale for our study is insufficient data on T and NK cell immunity in patients with hyperglycemia after COVID-19. The study was aimed at the features of T cell immunity in individuals with post-COVID syndrome and disorders of carbohydrate metabolism, depending on the NK cells count. Materials and methods: Sixty-four post-COVID patients with carbohydrate metabolism disorders were divided into three groups: with reduced, normal, or elevated NK cell counts. Carbohydrate metabolism disorders included impaired glucose tolerance (n = 36) and type 2 diabetes mellitus (n = 28). The comparison group comprised 60 post-COVID persons with no history of carbohydrate metabolism disorders. The assessment of the lymphocytic link of immunity included the definition of: CD45⁺CD3⁺ (T lymphocytes), CD45⁺CD3⁺CD4⁺ (T helpers), CD45⁺CD3⁺CD8⁺ (T cytotoxic), CD45⁺CD3⁺CD16⁺CD56⁺ (T-NK cells), CD45⁺CD3^-CD16⁺CD56⁺ (natural killers), CD45⁺CD3⁺CD4⁺CD25⁺ (T lymphocytes – early activation), CD45⁺CD3⁺HLA-DR⁺ (T lymphocytes – late activation). Results and Discussion. As the study showed, a decrease in the number of natural killers was accompanied by a higher level of T helpers in the group with carbohydrate metabolism disorders, the latter is probably associated with a compensatory increase in T lymphocytes and dysregulation of the T cell link of the immune system. It can also be concluded that in patients with long-COVID and CMD, with normal NK cell counts, an altered subpopulation composition remains, namely, a significant increase in total T lymphocytes. Many authors associate the obtained data on a significant decrease in T-NK lymphocytes with a decrease in the antiviral activity of the immune system, which can lead to a poor response to new viral agents or contribute to the activation of chronic viral infections. Dysregulation of the T cell link in individuals with long-COVID and disorders of carbohydrate metabolism requires a more detailed study, including an assessment of the cytokine profile in this category of patients.

The mechanism of hepatocellular liver damage after COVID-19 is a multifactorial process. The most widely discussed causes are cytolytic liver damage due to the inflammatory response after COVID-19, drug-induced hepatotoxicity and direct cytotoxic effect of the virus. There are observations that SARSCoV-2 infection causes hepatitis B virus reactivation, but little has been described about the interaction between hepatitis C virus and SARS-CoV-2. The course of coronavirus infection is associated with marked expression of proinflammatory cytokines, participants in the multisystem inflammatory response, IL-1β, IL-6, IL-8, IL-18, MCP-1, TNFα, which contribute significantly to the observed early and late liver function impairment. The aim of the study was to evaluate the role of proinflammatory cytokines (VEGFA, IL-8, IL-6, MCP-1, TNFα, IL-18) as additional markers of hepatotoxicity after COVID-19. The study was performed between March and August 2022. Patients were divided into 2 groups: Group 1 – with increased aminotransferases against the background of treatment from COVID-19 and/or in the following 3-6 months after the disease without viral liver damage (n = 42), Group 2 – patients with co-infection (chronic viral hepatitis C (HCV) and COVID-19 (n = 26). The levels of cytokines – VEGF-A, IL-6, IL-8, MCP-1, IL-18, TNFα in blood serum were estimated by enzyme immunoassay method. Statistical analysis was performed using StatTech v. 3.1.4. The results of the study revealed a comparable increase in the level of transaminases and C-reactive protein in both groups, significantly different from the reference values. Direct correlations of moderate strength (linear Spearman correlation) were found between the following cytokines: TNFα-MCP-1 (R = 0.559; p = 0.001), TNFα-VEGFA (R = 0.400; p = 0.002), TNFα-IL-6 (R = 0.503; p = 0.001). We diagnosed a significant increase in serum VEGFA levels in group 1 patients (hepatotoxicity after COVID-19) (Me (Q_0.25-Q_0.75): 522 (250 to 1002), p = 0.001) and in group 2 patients (HCV + COVID-19) (Me 1196, Q_0.25-Q_0.75: (73 to 432). Similar trend with the level of IL-6, IL-8, exceeding the values of cytokines in healthy donors and significantly higher than in group 2 patients. Identified correlations between inflammatory cytokines prove unidirectional changes in the functioning of the regulatory network controlling immune virus-induced reactions.

The new coronavirus infection COVID-19, due to the complex pathogenesis of the disease, systemic impact on organs, the development of complications and persistent disorders after the infection, remains an important medical problem. Every year the number of patients with postcovid syndrome in need of timely and full rehabilitation is increasing. Recently, isolated work began to appear on the use of interval hypoxytherapy for the treatment of patients with coronavirus infection. The purpose of our study was to identify the long-term results of the effect of interval hypoxytherapy on the immunological and coagulation status of patients after suffering coronavirus infection COVID-19. 170 patients aged 45 to 59 years were examined after a moderate coronavirus infection before, after and three months after interval hypoxytherapy. The number of lymphocytes, immunoglobulins A, M, G, E and cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNFα) in blood, blood D-dimer, prothrombin time, fibrinogen in blood, antithrombin III, C-reactive was determined protein and ferritin in the blood. The conducted studies revealed changes in immunological reactivity after the coronavirus infection COVID-19, requiring correction. Interval hypoxytherapy had an immunomodulatory effect and led to the normalization of the main immunological parameters, which remained three months after hypoxytherapy: there was a significant (p < 0.05) increase in the number of CD3⁺T lymphocytes, CD4⁺T lymphocytes, CD8⁺T lymphocytes. The improvement in immune status was also evidenced by the normalization of the immunoregulatory index, an increase in the level of immunoglobulins A and G. The decrease in immunoglobulins E in the blood was an indicator of a decrease in the severity of sensitization of the body. The course of hypoxytherapy led to a decrease in the content of pro-inflammatory cytokines: IL-1β, IL-2, IL-6, IL-8, TNFα and an increase in anti-inflammatory cytokines: IL-4 and IL-10 in the blood, which indicated an attenuation of the inflammatory process in the lung tissue and in the body as a whole. Blood ferritin decreased 3 months after hypoxytherapy. As studies have shown, the effect of hypoxytherapy persists for three months after the course of treatment. Thus, interval hypoxytherapy can be recommended for the rehabilitation of patients after a moderate coronavirus infection. A repeated course of hypoxytherapy may be performed three months after the first course of hypoxytherapy.

The key role of neutrophilic granulocytes (NG) in the pathogenesis of COVID-19 makes them new targets for therapeutic approaches and of influencing the course and outcome of the disease, restoring changes in the phenotype and functions of NG. Synthetic peptides or polypeptide complexes of action are the most promising in the treatment of COVID-19. Aim: to reveal the effects of the influence of the hexapeptide (HP) – Arginyl-alpha-Aspartyl-Lysyl-Valyl-Tyrosyl-Arginine on the phenotype of functionally significant NG subsets in moderate COVID-19.

The study examined patients 61 (57-71) years old (n = 45) in the acute period of COVID-19 – study group1 (SG1). In vitro, samples SG1 were incubated with HP (10⁶ g/L, 60 min, 37 °C) – study group2 (SG2). The number of NG subsets was evaluated: CD16⁺IFNα/βR1⁺CD119⁺, CD16⁺IFNα/βR1⁺CD119^- , CD16⁺IFNα/βR1⁺CD119⁺, CD64^- CD16⁺CD32⁺CD11b⁺, CD64⁺CD16⁺CD32⁺CD11b⁺ and phenotype by membrane receptor expression density (MFI) (FC 500, Beckman Coulter, USA); NG phagocytic activity was tested before and after incubation with HP. The comparison group (GS) – of 22 volunteers examined in the pre-COVID period.

It was revealed that unidirectional effects of HP in vitro contributing to the restoration of the phenotype of subsets CD16⁺IFNα/βR1^- CD119⁺, CD16⁺IFNα/βR1⁺CD119^- to CG indicators. There was a decrease in MFI CD16 (p < 0.05) in both subsets; MFI CD119 (p < 0.05) in the CD16⁺IFNα/βR1^- CD119⁺NG subset, MFI IFNa/βR1 in the CD16⁺IFNα/βR1⁺CD119^- NG subset. The effects of HP on the phenotype of CD16⁺IFNα/βR1⁺CD119⁺NG subsets in 76% of cases were manifested by a decrease in MFI CD16 (p<0.05), an increase in MFI IFNα/βR1 and CD119 (p_{1, 2}<0.05), and in 24% of cases a decrease in MFI IFNα/βR1 (p<0.05). HP in vitro remodeling of the phenotypes subsets CD64^- CD16⁺CD32⁺CD11b⁺ and CD64⁺CD16⁺CD32⁺CD11b⁺ were established, providing the usefulness of effector functions from hyperactivated to normal. In the CD64^- CD16⁺CD32⁺CD11b⁺ subset, there was a decrease in MFI CD16 and CD11b to the indicators CG (p_{1, 2} < 0.05). Recovery of the NG phenotype under the influence of HP led to the restoration of the phagocytic function of NG.

Positive effects of HP in vitro on the phenotypes of subsets actively and NGfunctions in COVID-19 open up prospects for the creation of new methods of immunotherapy to restore NG dysfunctions.

The current direction of scientific research in recent years has been the study of the immunobiological properties of vitamin D. The purpose of this work was to analyze the results of oral administration of cholecalciferol in order to prevent infection with the SARS-CoV-2 virus in the first wave of the COVID-19 pandemic. The study was performed in the period from October 07 to December 29, 2020, when there were no immunobiological drugs for specific prevention of COVID-19. The total number of respondents was 73 people; all had been ill with coronavirus only once. The etiological diagnosis of the disease included molecular genetic testing of samples of two localizations obtained by the conventional method (nasopharynx, oropharynx). The concentration of antibodies to the virus was determined on average 2 months after the disease using a set of reagents SARS-CoV-2-IgG quantitative-ELISA-Best (JSC Vector-Best, Russia). An approximate assessment of IgM concentration was carried out using a set of SARS-CoV-2-IgM-ELISA-Best from the same manufacturer. Among the study participants were those who used immunobiological drugs for the prevention of infection (riamilovir, umifenovir hydrochloride monohydrate, human recombinant interferon alpha-2b, zinc acetate, vitamin C). In particular, 28 people (38.4%) took cholecalciferol (group No. 1) and 45 people (61.6%) did not use this (group No. 2). Statistical processing of the obtained data was performed using the statistical package STATISTICA v.12.5.192.5 (StatSoft, Inc., USA). We applied the analysis of basic statistics, Linear Discriminant Analysis, Kolmogorov–Smirnov test, Chi-Square test, Wald–Wolfowitz Runs Test, Kruskal– Wallis test.
Differences in the incidence of respiratory distress syndrome of the two studied groups were revealed: in patients taking cholecalciferol, the syndrome did not develop at all; in group No. 2, it was registered in 20.0% of cases (Chi-Square = 5.242, p = 0.02). In addition, in patients of group No. 1, the concentration of IgG 2 months after the disease was 3.8 times higher than the values in group No. 2 (Chi-Square = 9.268, p = 0.003). Similar differences were found for the IgM level (Wilks' Lambda: 0.659 approx. F (7.32) = 2.367 p < 0.045). It was known that in both groups there were respondents who used other immuno-active substances for preventive purposes. In the first group there were 18 people (24.7% of all); in the second, there were 13 people (17.8% of all). It was found that those who used other immuno-active substances and did not take vitamin D suffered the disease more easily than everyone else. The respondents who did not use any immunoprophylactic agents were the next in terms of the severity of the infection. The respondents who took cholecalciferol mainly assessed the severity of the infection as average. The study participants who took both vitamin D and used other means of prevention suffered the most from COVID-19. Respondents who took cholecalciferol more often than others reported long-term fatigue, exacerbation of chronic and the appearance of new diseases (hypertension, cardialgia, bronchial asthma, allergies, decreased visual acuity), muscle, joint and vertebral pains that appeared for the first time. The phenomenon of arthralgia and other lesions of large joints in COVID-19 was described by us earlier. Studies by other authors also report frequent complaints of increased fatigue and joint pain. At the same time, the role of vitamin D is considered exclusively from the standpoint of vitamin deficiency in a new coronavirus infection and its potential role in inhibiting hyperinflammatory reactions, as well as accelerating the healing process of affected areas, especially in lung tissue.
It was found that vitamin D intake did not affect the incidence of fever, the incidence of pneumonia, the volume of lung tissue damage (based on computed tomography data), the duration of hospitalization and the disease as a whole, and also did not prevent the development of anosmia and dysgeusia. The use of vitamin D as a protective agent to prevent infection with the SARS-CoV-2 virus has had an impact on reducing the frequency/ prevention of cases of respiratory distress syndrome during the disease. Also, those who took vitamin D recorded an increase in the formation of IgG to the SARS-CoV-2 virus 2 months after infection 3.8 times higher than the values recorded in respondents who did not take cholecalciferol. The participants who took cholecalciferol suffered the infection more severely, especially if they used any other protective substances. Also, with the preventive intake of vitamin D after COVID-19, increased fatigue persisted longer, the appearance of new and activation of chronic diseases and muscle, joint and vertebral pains that appeared for the first time were reported more often, which correlates with the data we received earlier.

Data on the role of regulatory T lymphocytes (Treg) in the immunopathogenesis of tuberculosis are actively accumulating in the current literature. The overwhelming effect of Treg cells on the proliferation, functional activity of Th1 lymphocytes and antigen-presenting cells allows to consider this population as a possible target of modulation of the immune response in patients with tuberculosis. The Notch signaling pathway participates in the regulation of FoxP3 transcription factor expression and, therefore, is capable of supporting suppressor activity of Treg lymphocytes. A key role in the functioning of the Notch signaling cascade belongs to the enzyme γ-secretase that cleaves the intracellular domain of the receptor (Notch ICD), with the subsequent formation of a complex that regulates cell differentiation. The actively studied inhibitor of γ-secretase is DAPT – N-[N-(3.5-difluorophenacetyl)-L-alanyl]-S-phenylglycine tert-butyl ester). Mononuclear leukocytes isolated from the blood of patients with drug-sensitive and drug-resistant pulmonary tuberculosis by gradient centrifugation before the start of anti-tuberculosis therapy were used as the material for the study. The cells were cultured under conditions of stimulation with Mycobacterium tuberculosis antigens CFP10-ESAT6 or with the addition of γ-secretase inhibitor (DAPT) at doses of 5 μM/L and 10 μM/L in combination with CFP10-ESAT6 at 37 °C and 5% CO₂ for 72 h to the incubation medium. The number of Treg lymphocytes was assessed by flow cytofluorimetry by determining the expression of the CD4 surface receptor (FITC) and the intracellular transcription factor FoxP3 (PE). In intact cell cultures of pulmonary tuberculosis patients, the relative number of Treg lymphocytes was statistically significantly (p < 0.001) higher than that of healthy donors. Stimulation of cells with CFP10-ESAT6 antigens was accompanied by an increase in the proportion of CD4⁺FoxP3⁺ cells in both groups of tuberculosis patients. Addition of γ-secretase inhibitor at a concentration of 5 μM/L to the incubation medium did not lead to statistically significant changes in the number of Treg lymphocytes. The increase in DAPT concentration up to 10 μM/L was accompanied by a decrease in the number of Treg lymphocytes in comparison with the corresponding indices upon stimulation with CFP10-ESAT6 antigens in all groups of the subjects. Regardless of cultivation conditions, the number of CD4⁺FoxP3⁺ cells in patients with drug-resistant mycobacteria exceeded their number in patients with drug-sensitive pulmonary tuberculosis. Inhibition of the Notch signaling pathway by a γ-secretase inhibitor (DAPT) at a concentration of 10 μM/L contributed to a decrease in the number of Treg lymphocytes in patients with drug-sensitive and drug-resistant pulmonary tuberculosis. Reduction of Treg lymphocyte number by γ-secretase inhibitor confirms the importance of Notch signaling cascade as a potential target for correction of Treg lymphocytes immunosuppressive activity and pathogenetic therapy of tuberculosis. 

Infection with hepatitis C virus (HCV) is common among HIV-positive patients, with up to 50% of them being coinfected in Russia. While highly active antiretroviral therapy (HAART) suppresses HIV replication and restores the immune system of HIV-infected subjects, HCV coinfection interferes with CD4⁺T cell regeneration and increases the risk of patients’ morbidity and mortality. During HAART, HIVinfection progression and the immune system restoration efficiency largely depend on immune activation and CD4⁺T cell exhaustion. This study determined the level of activation, exhaustion, and cytokine production in CD4⁺T cells obtained from the peripheral blood of HAART-treated HIV/HCV coinfected and HIV monoinfected subjects. The study comprised 11 HIV/HCV coinfected individuals and 10 HIV monoinfected patients receiving HAART for more than two years, with a control group of 10 volunteers without the signs of HIV or HCV infections. Compared with healthy controls, HIV/HCV coinfected patients had an increased frequency of activated CD38⁺HLA-DR⁺ CD4⁺T lymphocytes (p < 0.05), a higher level of CD4⁺T cell exhaustion determined according to the TIGIT expression density per cell (p < 0.05), and a greater proportion of interferon-gamma (IFNγ)-producing CD4⁺T lymphocytes following activation (p < 0.05). The frequency of IFNγ-producing CD4⁺T cells in the donors’ blood positively correlated with the proportion of activated CD4⁺T cells (R = 0.514, p < 0.01). Despite having a large number of IFNγ-producing CD4⁺T lymphocytes, the HIV/HCV coinfected patients’ average production of IFNγ by CD4⁺T cells was significantly lower than that in healthy controls (p < 0.05). The IFNγ production in CD4⁺T lymphocytes did not depend on activation (p > 0.05). However, a negative correlation was established between the IFNγ production and the level of CD4⁺T cell exhaustion (R = -0.400, p < 0.05). The letter was also found to inversely correlate with the CD4⁺T cell counts in the donors’ peripheral blood (R = -0.598, p < 0.01). These data suggest that HCV coinfection leads to pronounced functional exhaustion of CD4⁺T cells and may aggravate the course of HIVinfection in patients receiving HAART.

Despite successful suppression of viral replication by antiretroviral drugs there is no significant increase in the number of peripheral CD4⁺T lymphocytes in some HIV-infected patients (immune nonresponse to therapy). One of the crucial factors for immunodeficiency aggravation is immune activation developing in response to the bacterial products entry into the bloodstream through the damaged intestinal barrier. Additionally, the intestinal microflora produces various solutes that accumulate in the blood and exhibit toxic properties. This work aimed to evaluate the effect of intestinal microbial products (para-cresol sulfate and indoxyl sulfate) on the number of CD4⁺T lymphocytes in HIV-infected patients receiving antiretroviral therapy. The object of the study was the peripheral blood of HIV-infected subjects with different immune system restoration efficiency during the therapy. Uninfected donors were enrolled as healthy controls. Plasma concentrations of IL-6 (p = 0.012), IP-10 (p = 0.0004), and sCD14 (p = 0.003) in HIV-infected immune nonresponders were increased compared with those in individuals with effective restoration of CD4⁺Tcells (immune responders). Although both groups of HIV-positive subjects did not differ in plasma lipopolysaccharide and I-FABP levels, para-cresol sulfate (p = 0.001) and indoxyl sulfate (p = 0.042) concentrations were increased in immune non-responders. In vitro experiments showed a negative dose-dependent effect of para-cresol sulfate and indoxyl sulfate on the viability and mitotic activity of CD4⁺T lymphocytes. Thus, in HIV-infected patients with impaired regeneration of CD4⁺T lymphocytes during antiretroviral therapy, a higher level of systemic inflammation is noted than in subjects responding to treatment with an increase in the number of CD4⁺T cells. The severity of the intestinal barrier damage and the load of bacterial components released into the bloodstream are approximately the same in HIV-infected individuals with different efficiency of immune recovery in response to treatment. Simultaneously, the blood plasma of immune non-responders is significantly enriched with microbial products of intestinal origin: para-cresol sulfate and indoxyl sulfate. The significant decrease in the proliferative capacity of CD4⁺T cells stimulated in vitro and the induction of their death in the presence of these toxins may be a reason for the ineffective restoration of the number of CD4⁺T lymphocytes in HIV-infected individuals receiving antiretroviral therapy.

Currently, the available methods of treating parodontitis are not able to have a complex effect. Therefore, in recent years, there has been an active search and development of new methods of treatment and new drugs that have a complex etiopathogenetic effect on this disease.
This article provides a comparative evaluation of the classical and experimental methods of treating chronic periodontitis. Based on the reconstruction of an experimental model of chronic inflammation of periodontal tissues of the Wistar rat line, we compared methods of topical therapy by “Organosilicon Glycerohydrogel – Peptide” and “Polyoxidonium” compositions. A comparative assessment of the activity of these drugs with control groups, which were treated with “Organosilicon Glycerohydrogel” and “Metrogyl Denta”, was carried out.
Previously, we carried out separate studies of the effectiveness of the use of the composition “organosilicon glycerohydrogel – peptide”, as well as the method of treatment of periodontitis, by injecting the drug “Polyoxidonium”. They have been compared with the classic treatment for this disease to obtain relevant data and results.
In our opinion, the data obtained are of considerable interest. The assessment and comparison of clinical and histological data have been carried out, which showed that all drugs had a positive effect on the processes of tissue regeneration. However, the composition “Organosilicon Glycerohydrogel-peptide”, due to the characteristics of the hydrogel, which is acting as a transcutaneous conductor, showed a faster antimicrobial and pathogenetic effect, which allows a comprehensive approach to solving this problem. In comparison with the groups of “Organosilicon Glycerohydrogel” and “Polyoxidonium”, the period of clinical improvement increased by 57% in the group of “Glycerohydrogel-Peptide”, and, in the “Metrogyl Denta” group, the indicators improved by 15% approximately.

Chronic pelvic inflammatory disease (PID) in women remains a problem due to the importance of medical consequences. The study of the receptor apparatus of neutrophilic granulocytes (NG) involved in anti-infective protection in diseases of various etiologies seems to be relevant. Aim: to clarify the features of variants of quantitative and phenotypic changes in subsets of NG CD11b⁺CD64^-CD32⁺CD16⁺, CD11b⁺CD64⁺CD32⁺CD16⁺ of immunocompromised women during exacerbation of chronic PID of various etiologies. We were tested women 20-40 years: Study Group 1 (SG1, n = 20) – chronic PID during the exacerbation with mono- or mixed latent/recurrent various viral infections (chronic herpes-virus infections, papillomavirus infection, recurrent ARVI); Study Group 2 (SG2, n = 30) – chronic PID of bacterial etiologies; Comparison Group (CG)– 20 healthy women. The number of subsets CD11b⁺CD64^-CD32⁺CD16⁺NG (major) and CD11b⁺CD64⁺CD32⁺CD16⁺NG (minor), receptor expression density (MFI) was determined (FC500, USA). It was found that in PID during the period of exacerbation, diagnostically significant differences in the subset composition of NG were revealed. We got a decrease in the CD11b⁺СD64^-СD32⁺СD16⁺NG subset and in 7,6 times increase in the CD11b⁺CD64⁺CD32⁺CD16⁺NG subset in SG2 with chronic PID of bacterial etiology, in contrast to chronic PID occurring in combination with recurrent/persistent viral infection SG1. Negative transformation of NG subsets is associated with a predominant decrease in the level of expression of the activation CD16. The absence of an adequate response to the infectious and inflammatory process was revealed – the absence of an increase in the expression of the activation CD11b in the major subset in SG1, as well as in the minor subset in groups SG1 and SG2. In the major subset of NG in groups SG2 a decrease in the expression of the activation marker CD11b. In the various viral infections and PID (SG1), in the negatively altered minor subset of NG we got a decrease of expression of CD16, an increase of expression of CD64 and CD32. Determination of subsets of CD11b⁺СD64^-СD32⁺СD16⁺, CD11b⁺CD64⁺CD32⁺CD16⁺NG and their phenotype can be used as diagnostic markers for the differential diagnosis of PID of viral and bacterial etiology, and for the development of new methods of targeted immunomodulatory therapy.

The reproductive potential of both women and men is declining every year. Many factors contribute to the violation of the reproductive function – chemical, physical, mechanical, psychogenic, however, biological factors have the most pronounced effect on reproduction. Chronic viral cervicitis can be not only the cause of infertility and reproductive losses, but also the development of intraepithelial dysplasia, as well as cervical cancer. PVI, as a monoinfection, is quite rare along with HPV. Other UGIs (urogenital infections) act as common routes of transmission and entry gates. The most common association with PVI is herpesvirus infection. An increase in MMP, both systemically and at the local level, may indicate a violation of cell modeling processes, which contributes to the development of autoimmune inflammation with further destruction of the tissues of the reproductive tract. Activation of MMP promotes the release of HSV from the nerve ganglia and reactivation of the infection. Therapy for HPV and HVI (herpes virus infections) are debatable. There is no single standard of treatment, but there are a number of drugs that have antiviral and immunomodulatory effects. Currently, there are no studies on the dynamics of the effect of HPV and HSV infection on the state of MMPs and TIMPs during Inosine pranobex therapy. Objective: to evaluate changes in matrix metalloproteinases 2 and 9 and their tissue inhibitors types 1 and 2 in patients with human papillomavirus and herpes infections after Inosine pranobex therapy.
6 patients with papillomavirus and herpetic infections were examined and treated with drugs containing the active ingredient Inosine pranobex. The levels of MMP-2, MMP-9 and TIMP-1, TIMP-2 in blood serum were determined using specific reagents from R&D Diagnostics Inc. (USA).
The dynamics of indicators in the blood serum of patients with PVI showed a decrease in the level of MMP-2, MMP-9, TIMP-1 with a simultaneous increase in TIMP-2 relative to the values before therapy. In patients with PVI and HVI, Inosine pranobex therapy showed a decrease in MMP-2 and MMP-9 levels, no changes in the content of TIMP-1, but an increase in the serum content of TIMP-2. Prior to the use of therapy, an increase in the ratio in the main groups in comparison with the control group was found, however, the largest increase was found in the group with the association of infections. After therapy, positive dynamics was established in the main groups. Thus, the ratio in group I decreased and became equal to the control values. In the II group of patients, the ratio, despite the decrease, remained higher than the control values and higher in comparison with the I group of women.

Periprosthetic joint infection still remains a clinical challenge since accurate definition of this condition and reliable laboratory markers have not been established yet. This study aimed to evaluate the benefit of some lymphocyte and monocyte subset determination in patients with periprosthetic joint infection and non-infectious arthroplasty failure. Thirty-four patients with chronic periprosthetic joint infection, 12 patients with non-infectious arthroplasty and 30 healthy persons were included in the study. The counts of CD3⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, CD19⁺, CD3^-CD16⁺CD56⁺, CD3⁺HLA-DR⁺, CD4⁺CD45RACD45RО⁺, CD4⁺CD45RA⁺ CD45RО^- and CD14⁺ HLA-DR⁺ subsets in peripheral blood were assessed by flow cytometry. The assessment of the intensity of antigen expression was carried out according to mean fluorescence intensity. A significant increase in CD3⁺CD4⁺ subsets (p < 0,01) and a significant decrease in CD3-CD16⁺CD56⁺ subsets (p < 0,005) were revealed in patients with periprosthetic joint infection compared to the healthy controls. The content of CD19⁺ lymphocytes in these patients was significantly higher than in aseptic ones (p < 0,005); the latter group was also characterized by more pronounced increase in the number of activated T lymphocytes (CD3⁺HLA-DR⁺) compared to controls (p < 0,001). Patients with periprosthetic joint infection showed decreased “naïve” T lymphocytes (CD4⁺CD45RA⁺CD45RO^-) count compared to aseptic ones (p < 0,05), and both groups showed a decrease counts compared to controls (p < 0,001). On the contrary, memory T lymphocyte (CD4⁺CD45RACD45RO⁺) count was significantly increased in both compared groups (p < 0,05). Patients with periprosthetic joint infection compared with other two groups demonstrated a significant decrease in the number of activated monocytes (CD14⁺HLA-DR⁺) and pronounced decrease in the expression intensity of this marker on cell membrane (p < 0,05 and p < 0,001, respectively). Thus, evaluation of lymphocyte and monocyte subsets, including expression of cell activation antigens could be useful as additional laboratory test in combination with other conventional methods for differentiation between periprosthetic joint infection and aseptic arthroplasty failure.

Traumatic damage to the anterior cruciate ligament leads to impaired support and mechanical instability of the limb. One of the frequent complications after injury is arthrogenic muscle inhibition due to inhibition of the quadriceps muscle and the development of functional contracture. On the contrary, one of the indicators of high muscle activity is a sufficient level in the blood of functional muscle proteins – myokines, in particular interleukin-6, which are expressed and released by muscle fibers. The aim of the study was to study the level of interleukin-6 in men with damage to the anterior cruciate ligament in the dynamics of electromyostimulation of the quadriceps femoris.
The study involved 23 men, mean age 34.8±2.2 years, with traumatic injury of the anterior cruciate ligament, who, 10 days before surgery, underwent electromyostimulation of the quadriceps femoris using the INTELECT® Advanced device (Chattanooga (DJO), USA). The control group consisted of 12 healthy men, mean age 32.2±2.4 years. The level of IL-6 was determined in the blood serum before electromyostimulation, and in dynamics using a kit for enzyme immunoassay (Vector-Best, Novosibirsk). The obtained data were processed using the Statistica licensed software package v. 10.0.
The basal level of IL-6 in the main group was 1.28 (0.87-1.72) pg/mL, which is significantly lower than in healthy individuals 5.2 (3.8-6.1) pg/mL and is due to a low level of physical activity due to functional contracture of the quadriceps muscle. In the dynamics of electromyostimulation on the 5^th day, the level of IL-6 significantly increased by 3.2 times from the basal level, on the 10^th day by 4.6 times, while not exceeding that of the group of healthy individuals. With the reduction of myocytes, the concentration of myokine interleukin-6 increased in the cytoplasm of cells, which contributes to the accumulation of macroergs in the muscle cell, due to myokine-dependent activation of glycogenolysis. The reparative and anti-inflammatory properties of IL-6 are realized in stimulated striated muscles by the classical signaling mechanism that can block the activation of the universal intracellular transcription factor NF-κB in relation to the production of pro-inflammatory cytokines. Thus, electromyostimulation before the start of surgical treatment leads to an increase in the concentration of myokine IL-6 in the blood, which contributes to an increase in the anti-inflammatory and reparative potential of damaged tissues.

 Severe mechanical injury is one of the main reasons behind children’s disability and mortality. Severe injury induces a complex host immune response to tissue injury, a parallel pro- and anti-inflammatory state, bearing an elevated risk for infectious complications (IC) and/or multiple organ failure (MOF). This study aimed to determine the informative immunological criteria of traumatic injury severity and prognosis outcome in children (severe injury group (SInj, ISS ≥ 16), n = 87; mild/moderate injury group (MInj, ISS < 16), n = 34) based on the assessment of absolute cell count (abs) and percentage of such T helper subpopulations as regulatory T lymphocytes – CD4⁺CD127^lowCD25^high(Treg), Th17 lymphocytes – CD4⁺CD161⁺ and CD4⁺CD127^higtCD25^high T cells(T127hi) in severe injury cases grouped by the outcome (favorable, n = 47; unfavorable, n = 40) and depending on IC (n = 16) and the development of MOF (n = 11) on the 1^st, 3^d , 5^th, 7^th, 14^th day after injury. The control group was comprised of 80 apparently healthy children comparable in age and sex. An inverse relationship between severity of injury, degree of blood loss and outcome of injury was revealed with the abs of all Th populations, but for Th abs and Treg abs the most significant correlation was found (Spearman’s R ≤ -0,70, p < 0.00001). For SInj group, a pronounced decrease of Th abs, Treg abs, T127hi abs and Th17 abs, in the acute post-traumatic period with an increase to 14 days was revealed. The values of in the first day for indicators of patients with MInj group correspond to the values of control group and significantly differ from SInj group. There are different kinetics of percentage Th subpopulations in peripheral blood of children with severe injuries. The Th17%CD4⁺ and T127hi%CD4⁺ significant increase in 1^st-3^d  and 3^d -7^th days after injury respectively in comparation with сontrol and MInj groups. There were no differences between groups in terms of Treg%CD4⁺. The lower-level Treg abs in trauma patients admitted to the ICU is significantly associated with develop the infectious complications and outcome of trauma. The Th17 abs is significantly reduced in 3-7^th days after the injury in the SInj group with MOF. The results of the study indicate that in children levels of Treg, T127hi and Th17 is significantly associated with severity of injury and may be used to predict outcome of trauma and assess the risk of IC and MOF.

Osteomyelitis is an inflammation of bone and bone marrow caused by the spread of S. aureus from a local focus by the hematogenous route or from an open traumatic fracture; it is difficult to treat and remains a serious problem. The condition for spreading of the infectious process into bone is the effect of S. aureus and its impaired elimination due to immune system (IS) dysfunction. Controversial information on the immunopathogenetic mechanisms of acute osteomyelitis needs study, which would allow the development of sound immunotherapy. Purpose of the study: to specify the variants of antibacterial immune protection disorders in children with acute hematogenous and acute posttraumatic osteomyelitis. Materials and methods. Children 8-15 years old (n = 22) were studied: Study Group 1 (SG1, n = 12) – with acute hematogenous osteomyelitis (AHO); Study Group 2 (SG2, n = 10) – with acute post-traumatic osteomyelitis (APTO). The comparison group (CG) – 13 healthy children. Tested: Tlymphocytes (CD3⁺CD19^- , CD3⁺CD4⁺, CD3⁺CD8⁺), B lymphocytes (CD3^- CD19⁺), NK (CD3^- CD16⁺CD56⁺) and TNK (CD3⁺CD16⁺CD56⁺) lymphocytes, neutrophil granulocytes (NG, CD16, CD32, CD64) (FC-500 Beckman Coulter, USA); the level of serum IgA, IgM, IgG (ELISA). Phagocytic function of NGs in relation to S. aureus was assessed: the number of actively phagocytizing NGs (%PhAN), capture processes (PhN, PhI) and killing activity (%D, DI). Results. In both groups was revealed a decrease of T lymphocytes, T helpers, T_CTL and NK quantity (p_1-4 < 0.05). In AHO, the levels of IgA, IgM, IgG did not differ from that in GS, while in APTO the levels of IgA and IgG increased (p_{1, 2} < 0.05). The density of CD64, CD16, CD32 receptor expression on NG in the studied groups has been a different equipping, predetermining an incompetence of the phagocytic function: in AHO associated with abnormalities in the function capture and killing, in APTO only with the S. aureus digestion. Conclusion. The revealed combined defects of IS functioning necessitate the development of new approaches in the treatment of AHO and APTO in children, pathogenetically substantiating the use of immunotherapy in the complex etiopathogenetic treatment. This approach will contribute to the restoration of mechanisms of anti-infective immunity, timely elimination of pathogens, improve the clinical course of the diseases, prevent the chronic inflammatory process.

Inclusion of neutrophilic granulocytes (NG) in inflammation depends on the expression of receptors providing the functions of NG. Acute osteomyelitis (AOM) occupies a central place among purulentinflammatory diseases in children. AOM purulent-necrotic process proceeds in the bone, bone marrow – the site of hematopoiesis. It is interesting to determine the functionally significant NG subsets, their phenotype in OM and evaluate the effect of immunotropic substances for the correction of dysfunctions. Aim: to specify the variants of changes in quantitative and phenotypic characteristics of CD66b⁺CD16⁺CD33⁺HLA-DR^-, CD66b⁺CD16⁺CD33⁺HLA-DR⁺ NG subsets at AOM in children and evaluate the possibility of their immunomodulation under the influence of hexapeptide (HP) – Arginyl-alpha-Aspartyl-Lysyl-Valyl-Tyrosyl-Arginine in vitro.

Peripheral blood (PB) of 24 children 8-15 years old AOM were the study group (SG). The comparison group (CG) – 13 healthy children. HP (10^-6 g/L) were incubated with PB SG (60 min, 37 °C) to evaluate the effects (SG1). The number of NG subsets CD66b⁺CD16⁺CD33⁺HLA-DR⁺, CD66b⁺CD16⁺CD33⁺HLA-DR^- (FC500, Beckman Coulter, USA), receptor expression density (MFI), phagocytic activity before and after incubation with HP were determined.

The NG subset expressing HLA-DR – 29.9 (18.4-43.6) % CD66b⁺CD16⁺CD33⁺HLA-DR⁺ was registered in children with AOM. The number of CD66b⁺CD16⁺CD33⁺HLA-DR⁺ was 1.5 times lower (p > 0.05), of CD66b⁺CD16⁺CD33⁺HLA-DR⁺ was 1.2 times higher (p > 0.05) than before incubation with of HP. The redistribution of subsets apparently occurs due to the binding of HPs to HLA-DR on the NG membrane. Also MFI HLA-DR was low (p > 0.05); the 1.3-fold increase in MFI CD66b, 1.4-fold decrease in MFI CD16 were revealed (p < 0.05).

The study was the first to demonstrate the presence of NG subset of CD66b⁺CD16⁺CD33⁺HLA-DR⁺ in the PB of children with AOM. Subset of CD66b⁺CD16⁺CD33⁺HLA-DR⁺NG in AOM indicates the appearance of an activated subset of NG in PB with the properties of APC. The positive influence of HP on the phenotypic characteristics of subsets СD66b⁺CD16⁺CD33⁺HLA-DR^-, СD66b⁺CD16⁺CD33⁺HLA-DR⁺. Restoration of phagocytic function of NGs under the influence of HP is connected with the increase of CD66b expression, which influences the effector function of NGs and decrease of CD16 molecule hyperexpression that stipulates decrease of damaging cytotoxic activity of NGs.

The article is devoted to the development of immunological indicators of intestinal inflammation in children, which is of great importance for health authorities when organizing specialized pediatric and surgical services. The proposed method contributes to the early diagnosis and prevention of complications of inflammatory surgical bowel diseases in children, which is of great practical importance.
The purpose of the study: To develop immunological indicators of complications of surgical bowel diseases in children.
A retrospective analysis of 867 case histories of children who received inpatient treatment at the Department of Pediatric Surgery of the Bukhara branch of the Republican Scientific Center of Emergency Medical Care from 2019 to 2022 for surgical diseases of the gastrointestinal tract was carried out.
The authors conducted an immunological study of 91 pediatric patients. All children underwent immunological blood tests: cellular and humoral immunity, cytokines (TNFα, IFNα, IL-8, MCP-1 and vascular endothelial growth factor VEGF-A) were studied. For the prevention of postoperative complications of CKD in children, it is recommended to determine IFNα in the blood serum in the period before surgery to solve the indications for immunocorrection. A noticeable positive relationship was established between IFNα and CD8 – r = 0.34, between IFNα and CD23 – r = 0.38, between IFNα and IgA – r = 0.39, between IFNα and PCT – r = 0.36. At the same time, PCT has a noticeable negative relationship with CD16 – r = -0.31 and with CD8 – r = -0.31 against the background of a noticeable positive relationship with IgG – r = 0.32 and IFNα – r = 0.36. It was found that IFNα is a more informative indicator of the effectiveness of the immune response, and PCT is an indicator of the effectiveness of antibacterial therapy in surgical bowel diseases in children

Gastroesophageal reflux disease (GERD) is a common acid-dependent disease among the population, including children, with multifactorial genesis. It, like many other acid-dependent diseases (peptic ulcer, etc.) is associated with a family predisposition to the disease. Of interest is the study of the role of cytokines in the regulation of pathology in childhood, depending on the severity of a family history of peptic ulcer disease. Aim: to evaluate the levels of cytokines in the blood serum in case of family history of ulcerative diseases in schoolchildren with gastritis associated with GERD. In the course of a scientific study, 142 children with gastroenterological complaints aged 7-17 years were examined. The diagnosis of GERD was made in the presence of weekly heartburn in accordance with the global consensus on pathology in children. All subjects underwent gastroscopy with taking biopsy material from the gastric mucosa and morphological confirmation of their diagnosis of gastritis in accordance with the Sydney classification. The concentration of cytokines in blood serum (IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, IL-1β, IFNα, TNFα) was obtained by enzyme immunoassay. During statistical processing, the χ²  and Mann–Whitney tests were used. The studies were approved by the ethics committee and informed consents of patients and their parents were obtained prior to the start of the study. The results of the study did not show significant differences in the concentration of cytokines in schoolchildren depending on the presence of GERD. In children with a family burden of peptic ulcer, GERD was detected more often (p = 0.054), which is probably a consequence of their increased acid formation. Changes in the cytokine profile of the blood were noted. During GERD, with aggravation of peptic ulcer, there was an increase in the replication of IL-4 (p = 0.027) and IFNα (p = 0.001). The increase in blood IFNα in children with GERD with family burden is obviously aimed at enhancing immune responses involving the whole body to damage. This is due to its functional role – participation in the immune response. Increased replication of IL-4, obviously, provides an increase in metabolic, immune processes in the body aimed at optimizing the course of proliferative processes in the esophageal mucosa under conditions of increased secretion of hydrochloric acid in the stomach. Thus, when a family history of peptic ulcer is aggravated in schoolchildren with gastritis associated with GERD, a number of links in the cytokine network (IL-4, IFNα) move to the systemic level of regulation.

When the body is infected with the bacterium Helicobacter pylori, a cytokine cascade is launched, which plays a key role in the progression of chronic inflammatory and destructive processes in the gastric mucosa. Thus, the secretion of a number of cytokines is stimulated, which in turn contribute to the attraction of immunocompetent cells and the development of inflammatory changes. However, hyperproduction of cytokines can lead to atrophic changes in the gastric mucosa and, as a result, degeneration into gastric cancer. Thus, the role of cytokines in precancerous conditions is ambiguous. On the one hand, they activate the immune response aimed at eliminating the pathogen. On the other hand, they themselves contribute to the progression of the disease.

The complex clinical and laboratory study included patients: 60 with chronic gastritis (CG), 55 with chronic atrophic gastritis (CAG), 50 with gastric cancer (GC, stage I-II, morphological variant – adenocarcinoma) and 60 – control group. The diagnoses were verified according to international and Russian recommendations and confirmed by laboratory and instrumental studies. All patients were comparable in terms of gender and age characteristics (p > 0.05). All patients had specific IgG to H. pylori. The study was approved by the Local Ethics Committee of the FRC KSC SB RAS (protocol No. 11 dated November 11, 2013). All ethical requirements were observed, and the patients signed the informed consent form for participation. Patients and persons of the control group underwent a single blood sampling from the cubital vein upon admission to vacutainers with heparin.

The levels of IL-2, IL-4, IL-8, TNFα, interferon-γ in the blood serum of patients and healthy individuals were determined using the enzyme immunoassay method using reagent kits manufactured by JSC “VectorBest”. Statistical data processing was carried out using the Statistica for Windows 8.0 application package.

All patients with H. pylori-associated diseases (CG, CAG, GC) showed an increase in pro-inflammatory (IL-2, IL-8, IFNγ) with a significant increase in IL-8 in all patients and IFNγ in gastric cancer and antiinflammatory cytokine (IL-4) with a maximum value in gastric cancer. A combined Th1 and Th2 is found – a mediated immune response with a maximum violation of cytokine regulation in gastric cancer.

The Helicobacter pylori bacterium is currently considered one of the leading etiopathogenetic factors in the formation of gastric and duodenal ulcer in children and adults. Despite many studies in this area, the mechanisms of phagocytic activity in response to exposure to Helicobacter pylori are not completely clear. The aim of the work was to obtain results on the functional and metabolic activity of blood neutrophilic granulocytes in children with Helicobacter pylori-associated erosive and ulcerative lesions of the stomach and duodenum. The object of the study are neutrophilic granulocytes isolated from the blood of patients and the control group. Samples were taken from 46 persons with Helicobacter pylori-associated erosive – ulcerative lesions of the stomach and duodenum aged 11 to 18 years and the control group, which consisted of 55 practically healthy persons who had this disease excluded in the same age range. A comparative analysis of the functional activity of cells using chemiluminescent analysis and metabolic activity by the bioluminescent method was carried out. Luminol was used as a chemiluminescence activator. The measurement of the functional activity of phagocytes was based on the determination of the base activity (spontaneous reaction) and the reserve capacity of the cells when they were exposed to the nonspecific inducer zymosan. There is a reduced activation index of neutrophils in patients relative to the control group, which may characterize reduced metabolic reserves of cells. In neutrophilic granulocytes, there is a decrease in G6PDG, an enzyme that triggers glycolysis along the pentose phosphate pathway and contributes to the reduction of nicotinamide adenine dinucleotide phosphate (NADP) to NADPH, which is necessary for the formation of reduced glutathione that binds oxidants. With its insufficiency, a decrease in the energy reserves of cells occurs. In neutrophilic blood granulocytes in children with erosive and ulcerative lesions of the stomach and duodenum with H. pylori infection, a decrease in metabolic reserves is observed, which is associated with inhibition of metabolic processes in cells.

The study aimed to evaluate the association between cyclic citrullinated peptide antibody seropositivity and chronic Helicobacter pylori (H. pylori) infection in patients with rheumatoid arthritis (RA). We examined 92 women with moderate RA activity. Serum antibodies to cyclic citrullinated peptide (antiCCP), antibodies to H. pylori (anti-H. pylori-IgG), and total antibodies to H. pylori CagA antigen (antiCagA) were determined by enzyme immunoassay; the presence of anti-CagA-IgG positivity was confirmed by immunoblot. 68.5% of RA patients were positive for anti-H. pylori-IgG, and 44.4% of patients in this group were positive for anti-CagA-IgG. All the study participants were divided into three groups: I – H. pylori seronegative (H. pylori^- ); II – H. pylori positive, CagA negative (H. pylori⁺/CagA^- ); III – H. pylori positive and CagA positive (CagA⁺). The anti-CCP values in RA patients with CagA⁺ (group III) were significantly higher not only in comparison with patients seronegative for H. pylori (p < 0.001), but also in comparison with patients from group II (H. pylori⁺/CagA^- ) (p = 0.041). A study of the influence of the RA activity, the presence of RF and H. pylori on anti-CCP content demonstrated a small proportion of anti-CCP variability (R2 = 0.09), with a high contribution of H. pylori (beta = 0.25). The addition of the CagA(⁺) index (beta = 0.503) to the presented model allowed us to describe the variability of anti-CCP in almost 30% of cases (R2 = 0.29). In the group of RA patients with anti-CCP values exceeding the established threshold value of 20 U/mL (normal index), there was an increase in the proportion of patients infected with H. pylori (p < 0.001), but not the proportion of CagA-positive patients (p = 0.06). When the threshold level was increased to 60 U/mL (three times the upper limit of normal) in patients with significantly high anti-CCP, the association with positivity for CagA became significant (p = 0.005). CagA is highly immunogenic and is capable of inducing an inflammatory response in the host that goes beyond the effect of H. pylori itself. Additional experimental studies are needed to investigate possible clinical and laboratory associations that may influence the treatment tactics of CagA⁺ patients with RA who are seropositive for anti-citrullinated antibodies, as well as to evaluate the possible effects of therapeutic intervention aimed at the eradication of H. pylori in this group.

Objective: To study the immuno-inflammatory markers of coronary heart disease, arterial hypertension and their combined course. The research work included 116 patients with cardiovascular disease of middle and old age. The average age of patients is 62.4±1.27. All patients were examined at the Bukhara branch of the Republican scientific and practical Center for emergency medical care. During the analysis, it was found that the level of systolic arterial blood pressure directly depends on the concentration of fibrinogen – r = 0.30 and oppositely depends on the concentration of procalcitonin (PCT) – r = -0.3 and IL-6 – r = -0.26. At the same time, a noticeable positive association of heart rate with creatinine in the blood – r = 0.35 was also revealed. The established connections show the contribution of inflammation syndrome (immune) in the progression of hypertension, or rather, indicators of the progression of hypertension in coronary heart disease are creatinine, fibrinogen, PCT and IL-6. Due to the high and noticeable correlation with the studied immuno-biochemical parameters of blood and functional parameters of the heart, IL-6 is a more informative indicator of the progression of coronary heart disease with the risk of complications and multiple organ failure. Thus, the established connections in our studies allow us to include the conclusion that, along with the above, risk factors for the development of rupture and/ or aneurysm of the aorta in CHD are an increase in the blood level of complement C3, IL-17 and PCT. Consequently, with an increase in the level of VEGF in the blood in CHD AS, the risk of an increase in the thickness of the LV in the diastole increases, and an increase in IL-6, IL-17A and urea in the blood shows a decrease in the thickness of the LV in the diastole, which makes it possible to differentiate the restrictive variant from the hypertrophic form in atypical angina. Due to the high and noticeable correlation with the studied immuno-biochemical parameters of blood and functional parameters of the heart, IL-6 is a more informative indicator of the progression of coronary artery disease with the risk of complications and multiple organ failure.

The postischemic inflammatory response plays a significant role in the pathogenesis of acute ischemic stroke (IS). It has been established that acute IS is accompanied by aseptic inflammation, which induces the activation of costimulatory molecules in the process of innate immunity response to brain tissue damage. The constantly progressive destruction of neuronal antigens contributes to an increase in the volume of the ischemic lesion. Evidence continues to accumulate indicating an important role of NLRP3-mediated inflammation in the pathogenesis of IS. It has been shown that autophagy is involved in the inflammatory cascade in acute IS. Many of the anti-inflammatory mechanisms mediated by autophagy in acute IS involve the key autophagic proteins Beclin-1, LC3, and p62. Experimental studies have shown that autophagy suppresses the activation of NLRP3 inflammation. Data on cross interactions between apoptosis and autophagy in the pathogenesis of IS are still controversial. The aim of the study was to evaluate the relationship between biomarkers of autophagy, inflammation, and apoptosis in the dynamics of the acute period of atherothrombotic IS. The article presents the results of a dynamic study of the serum concentration of the key autophagy biomarkers Beclin-1, LC3 and p62, apoptosis indicators Bcl-2 and p53, pro-inflammatory cytokines IL-1β, TNFα, IL-8, IL-18 which are involved in postischemic neuroinflammation. A statistically significant increase in the studied parameters was established in comparison with the control group. The maximum increase in the studied biomarkers is noted on the 1^st day after the development of ischemia in patients with a severe course of the disease. The relationship between autophagy activity, apoptosis biomarkers, and some indicators of the systemic inflammatory response in patients with moderate and severe atherothrombotic stroke was revealed. The results obtained confirm the literature data on the involvement of autophagy in the regulation of the postischemic inflammatory response.

The prevalence of atrial fibrillation is high and comparable in both sexes. Such factors as differently expressed blood biomarkers in women and men may play a role in the occurrence of atrial fibrillation and the development of thrombotic complications.
To study markers of inflammation and platelet activation in patients with atrial fibrillation of non-valvular origin, receiving anticoagulant therapy and having a history of thrombotic complications and patients with atrial fibrillation without thrombotic complications, depending on the gender of the patients.
The study included 22 healthy volunteers and 60 patients diagnosed with atrial fibrillation receiving anticoagulant therapy, of which 21 patients developed thrombotic complications. Serum levels of α2- macroglobulin, hsC-reactive protein, fetuin A, α-1-acid glycoprotein, L-selectin, serum amyloid P, adipsin, and platelet factor 4 were studied on FLEXMAP 3D using Acute Phase diagnostic test systems Panel 3.
A comparative study of the content of biomarkers demonstrated an increased concentration of C-reactive protein in men and women in both groups of patients with atrial fibrillation; decrease in fetuin A and L-selectin in the group of women with thrombosis compared with women without thrombotic complications and compared with healthy women. There were no gender differences in the concentration of fetuin A and L-selectin in the group of patients with atrial fibrillation without thrombotic complications and in healthy volunteers. The level of adipsin had no gender differences in the group of patients with atrial fibrillation with thrombosis and in healthy volunteers, however, it was significantly increased in women without thrombosis. The content of platelet factor 4 in women in both groups of patients exceeded the value of this indicator in healthy women; no gender differences were found in the groups of patients with atrial fibrillation.
Low levels of fetuin A and L-selectin, with a simultaneous increase in C-reactive protein and platelet factor 4, lead to an increase of prothrombogenic potential and to a change in the balance of pro- and antiinflammatory mediators towards increased inflammation in female patients with atrial fibrillation.

T regulatory lymphocytes (Treg) are present is adipose tissue. Their frequency, as well as the level of FoxP3 nuclear translocation, in epicardial and thymus adipose tissue remains unexplored. Properties of adiposeresident Tregs may be of high significance in patients with coronary artery disease as potential pathophysiological factor in the development of atherosclerosis. The aim of the study was to compare frequency of FoxP3⁺Tregs and FoxP3 nuclear translocation in epicardial, thymus, subcutaneous adipose tissue and peripheral blood in patients with coronary artery disease. A pilot study was conducted in 11 patients with coronary artery disease scheduled for the coronary artery bypass graft surgery after prior selective coronary angiography. Frequency of CD4⁺CD25^hiFoxP3⁺ and CD4⁺CD25^loFoxP3⁺ lymphocytes and FoxP3 nuclear translocation were evaluated by imaging flow cytometry in peripheral blood and in stromal vascular fraction of epicardial, subcutaneous and thymus adipose tissue. Frequencies of CD4⁺CD25^hiFoxP3⁺ and CD4⁺CD25^loFoxP3⁺ lymphocytes were higher in epicardial adipose tissue compared to blood (3 and 5 times higher, p = 0.020); CD4⁺CD25^loFoxP3⁺ cells frequency in subcutaneous adipose tissue was 4 times higher than in blood (p = 0.028). The level of FoxP3 nuclear translocation was the highest in blood and decreased in epicardial, subcutaneous and thymus adipose tissue (p = 0.020 both for CD4⁺CD25^hiFoxP3⁺ and CD4⁺CD25^loFoxP3⁺ lymphocytes). Frequency of CD4⁺CD25^loFoxP3⁺ cells was directly related to age in thymus (r_s = 0.818; p = 0.002), and inversely in epicardial adipose tissue (r_s = -0.618; p = 0.043). Frequencies of CD4⁺CD25^hiFoxP3⁺ and CD4⁺CD25^loFoxP3⁺ with FoxP3 nuclear translocation in subcutaneous adipose tissue negatively correlated with age (r_s = -0.827; p = 0.002 and r_s = -0.648; p = 0.031, respectively). Frequency of CD4⁺CD25^loFoxP3⁺ cells with FoxP3 nuclear translocation in thymus adipose tissue negatively correlated with waist-to-hip ratio (r_s = -0.700; p = 0.016). The severity of atherosclerosis was related only to the frequency of CD4⁺CD25^loFoxP3⁺ cells in subcutaneous adipose tissue (r_s = -0.655; p = 0.029). Thus, epicardial and subcutaneous adipose tissue are enriched with Tregs, but factors that influence Treg accumulation and FoxP3 nuclear translocation in these fat depots may be different. The obtained results may further be used for personalized immunomodulatory therapy in patients with atherosclerosis.

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias. Numerous data indicate a significant contribution of myocardial inflammatory changes in the development and progression of AF. The search for new laboratory biomarkers to assess the activity of myocardial inflammatory processes, and the study of their diagnostic significance for noninvasive diagnosis in patients with AF is relevant. Therefore, the aim was to study the features of the serum level of the biomarker Gal-3 and to identify its relationship with inflammatory changes in the myocardium in patients with AF. Depending on the results of histological studies, the patients were divided into 2 groups: group 1 – with morphologically verified active lymphocytic myocarditis (ALM), group 2 – with lymphocytic infiltration (LI). Analysis of the frequency of detection and severity of the inflammatory process in the myocardium showed that activity of 4-5 scores was detected only in group 1. In 2^nd group, activity of the inflammatory process in most patients was 1 score. All patients with LI mild interstitial inflammation were showed. In the ALM group moderate and severe interstitial inflammation was detected. A high number of CD3⁺ and CD45⁺ cells were found in 1^st group compared to group 2 (p < 0.001).

There were no significant intergroup differences in the serum level of Gal-3. At the same time, in 1^st group showed a significant decrease in Gal-3 in 6 months after treatment (p = 0.028). Positive correlations of Gal-3 with the severity of the inflammatory process and endocardial involvement were revealed in patients with ALM. The association of serum Gal-3 levels with CD68⁺ levels in 1^st group was detected (R = 0.48, p = 0.030). In 2^nd group, a correlation between the level of Gal-3 in 6 months after ablation with infiltration of CD45⁺ cells was found (R = 0.69, p = 0.003). Thus, in patients with AF and active lymphocytic myocarditis, significant associations were established between biomarkers of Gal-3 and inflammatory changes in the myocardium. This confirms the important role of Gal-3 as a participant in the inflammatory process.

Eotaxin is a chemokine, which is a chemoattractant mainly to eosinophils, as well as basophils and Th2 lymphocytes. According to studies, overexpression of eotaxin is found in endothelial and smooth muscle cells of blood vessels in the area of atherosclerotic plaque. In clinical medicine, cardio-ankle vascular index (CAVI) is widely used as an indicator of arteriosclerosis and a predictor of cardiovascular events. Few studies have shown the relationship of eotaxin with coronary atherosclerosis; in other studies, the relationship of eotaxin with atherosclerosis, myocardial infarction and pulse wave velocity was not revealed. The aim of the present study was to assess blood level of eotaxin and cardio-ankle vascular index and their association with major cardiovascular risk factors in patients with high and very high cardiovascular risk. We examined 65 patients with high and very high cardiovascular risk, due to documented coronary artery disease, type 2 diabetes mellitus, or combination of cardiovascular risk factors and who were undergoing generally accepted cardioactive, hypoglycemic therapy and lipid-lowering therapy. All patients were examined for the elastic properties of the vascular wall by volumetric sphygmography with assessment of CAVI. In the blood, the concentrations of eotaxin, high-sensitivity C-reactive protein, glycosylated hemoglobin and lipid spectrum indicators were determined. All examined were divided into two groups: with a normal value of CAVI (less than 8) and elevated. Patients with elevated CAVI had higher concentrations of eotaxin (p = 0.013), total cholesterol (p = 0.009), low-density lipoprotein cholesterol (p = 0.016), were older (p < 0.0001) and less likely to take statins (p = 0.002). In all those examined, correlations were found between serum eotaxin concentration and CAVI (r_s = 0.34; p = 0.005), as well as age (r_s = 0.32; p = 0.006). The age of the patients correlated with CAVI (r_s = 0.35; p = 0.007). Thus, in our study, we for the first time showed the relationship between higher concentrations of eotaxin and an increased cardio-ankle vascular index in patients with high and very high cardiovascular risk. Cardio-ankle vascular index was associated with age, lipid metabolism and lipid-lowering therapy. The obtained results allow us to consider eotaxin as a factor associated with atherogenesis and arterial stiffness.

Leukocyte-platelet adhesion during hypoxia, tissue damage, activation of inflammation and coagulation is associated with the expression of ICAM-1 membrane molecules and integrins by blood and tissue cells. At the same time, platelet adhesion receptors determine their adhesion to the endothelium and recruited lymphocytes. The role of platelets in the pathogenesis of ischemic cardiovascular diseases also consists in their ability to modulate both hemostasis and inflammatory reactions, which is accompanied by the secretion of inflammatory mediators and factors that promote the recruitment of leukocytes to tissue damage sites. Purpose of the study: to study the effect of the synthetic glucocorticoid dexamethasone on the expression of adhesion receptors CD18⁺ and CD54⁺ on leukocytes, the content of platelets and fibrinogen in the blood of patients with ALLI, the relationship of these indicators with the severity and outcome of the disease.

To study the effect of anti-inflammatory therapy, a group of 32 patients treated with dexamethasone was formed; the comparison group was represented by 71 patients with basic therapy, the control group consisted of 15 volunteers. After revascularization, all patients received antiplatelet and anticoagulant therapy. Dexamethasone infusions were carried out in a course of 4 to 6 days after reconstructive surgery. In all patients, the content of C-reactive protein in the blood, the content of platelets and fibrinogen were determined. The number of lymphocytes expressing adhesion molecules ICAM-1 (CD54⁺) and integrins (CD18⁺) was counted using the immunocytochemical method. Studies were performed before surgery and on days 1, 3, 7, and 10 after surgery.

With exacerbation of ischemia and damage to the endothelium, the accumulation of cytolysis products, the expression of adhesion molecules increases both on endotheliocytes and on inflammatory effector cells – leukocytes and platelets. Adhesion molecules conduct an activation signal inside the cell, which promotes adhesion of leukocytes and platelets to the endothelium, lymphocytic-platelet adhesion, the formation of a parietal thrombus, and possible occlusion of damaged vessels. Increased expression of adhesion molecules is associated with the activation of metabolism, inflammation, coagulation and oxidative stress, stimulates all hematopoietic lineages, including platelets. The level of involvement of cellular reactions in the pathogenesis of the disease affects the effectiveness and duration of treatment, the risk of recurrent thrombosis and death. Anti-inflammatory therapy with dexamethasone contributed to earlier remission, a decrease in the proportion of infectious complications, such as wound suppuration from 10% to 6%, the number of necessary amputations from 32% to 16%, the frequency of deaths from 31% to 6%, and a reduction in hospital stay from 13 days to 10.

Inflammation, adhesiveness of effector cells and thrombosis are important factors in the pathogenesis of acute lower limb ischemia. Therapy with dexamethasone helps to reduce the level of systemic inflammatory response, the number of necessary amputations, the number of complications and adverse outcomes in the treatment of ALLI, and reduce the length of stay in the hospital.

In recent years, researchers’ attention has been directed to the WNT signaling pathway study, which regulates embryogenesis processes and is involved in pathological condition development. The role of morphogenic proteins of WNT signaling pathway in the cardiovascular pathology genesis is practically not clear. The research aim was a comprehensive study of the main proteins of WNT signaling pathway (β-catenin, sclerostin, GSK-3α, GSK-3β, WIF-1 and DVL-1) in the blood serum of 353 patients with coronary artery disease acute forms who were treated at the Orel regional vascular center from 2019 to 2021, and 50 healthy individuals. A comprehensive analysis included an assessment of clinical, laboratory and instrumental parameters in the framework of current clinical guidelines, as well as an immunological examination to determine the morphogenic proteins of WNT signaling by enzyme immunoassay. The results showed a wide variability in the values of morphogenic proteins of WNT signaling pathway in the patient’s blood serum. The levels of β-catenin, WIF-1 and DVL-1 significantly exceeded those obtained in healthy individuals, while the concentrations of sclerostin and GSK-3β did not differ significantly from them. The level of GSK-3α of patients was twice lower than in healthy individuals. The highest sclerostin concentrations were found in patients with existing calcification of the aortic valve leaflets and aortic walls. Acute coronary syndrome unfavorable course was observed in patients with both extremely high and extremely low WIF-1 levels. Significant correlations were established between the level of morphogenic proteins of WNT signaling pathway and lipid metabolism, as well as myocardial remodeling. The obtained data on changes in the protein production of WNT signaling pathway allow us to expand our understanding of the molecular aspects of the immunopathogenesis of myocardial remodeling in coronary artery disease, increase the predictive potential for cardiovascular disease diagnosis and determine the vector for further development of cardioimmunology determination.

Ischemic stroke (IS) occurs as a result of local disturbance of hemocirculation and hypoxia in the brain tissue. Hypoxia-inducible factor-1α (HIF-1α), which is involved in the regulation of tissue oxygen levels, plays an important role in the pathophysiology of stroke, including neuronal survival, neuroinflammation, angiogenesis, glucose metabolism, blood-brain barrier permeability, and is important in IS outcomes. The purpose of the study was to determine the relationship between blood levels of HIF-1α and the degree of neurological deficit in the acute period of IS and the outcome of the disease. We examined 58 people with IS aged 73 (67-81) years. Patients were divided into two groups – discharged and dead. The severity of stroke (NIHSS), neurological deficit, comorbidity index, blood levels of HIF-1α, p53 protein, interleukin-6, cystatin C, CRP, creatinine, hematological parameters were determined at admission, on days 3 and 10 of the disease. At admission the blood levels of HIF-1α was lower than in the comparison group and remained reduced until the 10th day. On day 10 the association of HIF-1α with neurological deficit, comorbidity index and disease outcome was determined. We observed a feedback of HIF-1α with the content of erythrocytes, hemoglobin and hematocrit, which can be regarded as a reflection of the hemic component of mixed hypoxia. In dead patients, an increased blood level of cystatin C was detected, which was associated with HIF-1α concentrations. In all periods of observation of IS, a correlation between cystatin C and creatinine and CRP levels was noted. These results may indicate dysfunction of endotheliocytes, inflammation associated with hypoxia in IS. The prognostic significance of the blood level of HIF-1α on the 10th day for the outcome of IS was AUC = 0.900. Blood levels of HIF-1α in the acute period was associated with the severity of IS and the outcome of the disease.