The  establishment and  application of animal  models  represent effective  tools  for  research  in rheumatoid arthritis (RA) pathogenesis. Animal models that replicate various mechanisms reflecting all aspects of RA, including early RA pathology, have provided important insights into studying etiology and pathogenetic mechanisms of RA in humans. This review article was compiled in order to give an introduction to the current state of RA models.  Application of these  experimental disorders  for testing  potential therapeutic approaches will help to make better predictions for drug efficiency in human RA

Presence of myocardial infarction in patients with obesity can lead to an uncontrolled increase in proinflammatory cytokines and unfavorable course of the pathological process. Objective: to study the relationship of key inflammatory factors and the development of complications at different terms after myocardial infarction in patients with visceral obesity. The study involved 94 men with myocardial infarction. Visceral obesity was diagnosed by multi-slice computed tomography (LightspeedVCT 64 ,General Electric,USA). On the 1st and 12th day of hospitalization, we determined serum concentrations of interleukins (TNFα, IL-1β, IL-6, IL-8 IL-10 and IL-12), and C-reactive protein. Adverse cardiovascular events were documented during the next year. The most informative indicators were identified by a stepwise logistic regression analysis. In patients with myocardial infarction an imbalance of cytokine profile revealed, i.e., an increase in proinflammatory markers (TNFα, IL-1β, IL-6, IL-8, IL-12, CRP), along with decrease in IL-10, being more pronounced in cases of visceral obesity. Among the studied markers, closest relationship was observed between visceral obesity and serum concentrations of IL-6 and CRP. Over the year, adverse cardiovascular events proved to be more frequent in patients with visceral obesity. Post-infarction complication risk was associated with higher concentrations of IL-6, IL-12 and IL-10 deficiency. Hence, development of adverse cardiovascular events within a year after myocardial infarction is more typical to the patients with visceral obesity, and is accompanied by activation of proinflammatory cytokines and IL-10 deficiency.

Expression of Toll-like receptors (TLRs) on myeloid cells is of key importance for induction of systemic reactions caused by bacterial damage, and activation mechanisms of innate immune response. The study included thirty-six patients with sepsis in whom we assessed a prognostic value of TLR2, TLR4, CD14, HLA-DR expressed on monocytes, depending on severity of the disease and clinical outcomes. There were neither significant differences in TLR4 expression at all stages of clinical observation, nor correlations between expression of this marker on monocytes and severity of the disease, or outcomes of septic conditions. Low levels of MFI on monocytes TLR2, HLA-DR at 5 and 10 days, like as decreased expression of CD14 on 10th day of the disease were shown to be predictive for poor clinical outcomes of sepsis. 

We implemented bioluminescent technique to study the activity of NAD(F) – dependent dehydrogenase in lymphocytes separated from dark blood and lymphoid tissue in chronic adenoiditis. As a result of comparative analysis we revealed significant lowering of metabolic processes in blood lymphocytes and less expressed changes in adenoid tissue lymphocytes in chronic adenoiditis. We marked the lowering of energy and plastic processes in cell lymphocytes in blood and glucose anaerobic oxidation after their separation from adenoid tissue

Increased intrathecal synthesis and oligoclonal banding of immunoglobulins (Ig) in cerebrospinal fluid (CSF) are major immunological findings in multiple sclerosis. Free light chains are fragments of Ig molecules that are produced in parallel to oligoclonal Ig, and their production reflects total Ig synthesis within central nervous system. Assessment of intrathecal kappaand lambda free light chain production within CNS compartment will help to improve diagnosis and prediction of outcomes in multiple sclerosis. Concentrations of kappa and lambda free light chains and clonality of immunoglobulin pattern synthesis were studied in paired CSF and serum samples of 151 patients, including 92 patients with multiple sclerosis, and 33 patients with clinically isolated syndrome which later was transformed into the definite multiple sclerosis. A control group consisted of 26 patients with other inflammatory diseases of central nervous system. Several Ig parameters have been determined in the patients, i.e., Ig clonality in CSF; concentrations of free light chains (both kappaand lambda-) in CSF; as well as their indexes and ratios. It was established that synthesis of kappa free light chains were significantly elevated in patients with multiple sclerosis. Moreover, the amounts of free light Ig chains in patients with positive oligoclonality test were significantly higher than in cases without intrathecal oligoclonal synthesis. With respect to diagnostic significance, the kappa quotient proved the best available option for diagnosis of multiple sclerosis. Its combination with Ig oligoclonality assays caused a decrease in false-negative diagnostics by 42%. Diagnostic benefit of the kappa quotient could be also confirmed by the data of ROC analysis. Also concentration of lambda free light chains in cerebrospinal fluid showed a negative correlation with conversion terms of clinically isolated syndrome to evident multiple sclerosis. Therefore, the indexes of free Ig light chains enables more precise diagnostics, like as more efficient severity evaluation of multiple sclerosis. 

The article presents results of multiplex cytokine assays in blood serum and lacrimal fluid at the initial and intermediate stages of age-related macular degeneration (AMD). Some features of local and systemic disturbances in the cytokine profile were detected in these patients. It was revealed that the initial stage of AMD was associated with elevated IL-17 levels in lacrimal fluid, along with imbalance between the local increase and systemic decrease of TGF-β1 amounts. Intermediate-stage AMD was associated with increased levels of the most cytokines assayed (except of TGF-β1) in blood serum and lacrimal fluid, thus suggesting stimulation of both pro-inflammatory and angiogenic responses, like as activation of anti-inflammatory and anti-infective factors. 

 Significant incidence of chronic urogenital diseases, both of viral and bacterial origin in women of reproductive age leads to an increase in the frequency of intrauterine infections. These disorders lead to disturbances of postnatal adaptation of newborns and increased numbers of infectious complications. In order to assess the state of immune system, we examined forty-eight children born to women with urogenital infection, including twenty-nine infants with complicated course of early adaptation period (study group) and twenty children diagnosed as healthy upon discharge by the day 3 to 5 after birth (comparison group). By means of flow cytometry, the following subpopulations were assayed in cord blood: CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD3CD16+CD56+ cells, expression levels of markers specific to activated monocytes CD14 (HLA-DR), and lymphocytes (CD25+, CD69+), like as markers of functionally mature cells (CD45R0, CD45RA), both in total lymphocyte pool and among T cell populations. Contents of IL-1β, TNFα, IFNγ, IL-4, IL-6, IL-8, IL-10 were assessed by ELISA technique. Our studies have shown that umbilical cord blood samples from the main group of newborns showed a statistically significant decrease in relative content of CD3+, CD4+, CD8+ and CD4+CD25+ cells, along with increase in the absolute numbers of leukocytes and lymphocytes, B-cells and NK cells, as well as expression of CD45RO+, CD45RA+ and CD3+CD45RO+ receptors, CD69+ and CD14+HLADR+ activation markers, accompanied by a significant increase of IL-8 production. Numerical determination of CD45RO+, CD3+CD45RO+, CD69+ and CD14+HLA-DR+ cells, and IL-8 contents in newborns, may serve as prognostic criteria for assignment of risk group for early adaptation disturbances and development of infectious diseases. 

Cytokines are wide-range modifiers of biological reactions. Cytokine regulation provides proliferation, differentiation, cell function, cell-cell and inter-systemic interaction, direction and nature of immune response to invasion of infectious and non-infectious pathogens. There are several distinct groups of cytokines: pro-inflammatory, anti-inflammatory factors, regulators of cellular and humoral immunity etc. A distinct role of cytokines is not excluded for infectious complications accompanying multiple myeloma (MM). Cytokine regulatory effects on immune defense in the organism as a whole, and a balance between proand anti-inflammatory cytokines in blood of MM patients depend on the stage of multiple myeloma progression and possibility of infectious complications. Therefore, the aim of our study was to evaluate proand anti-inflammatory cytokines and cytokine regulation in patients with MM G-immunochemical option. Our study involved 101 patients with MM (IgG-variant), their age ranging between 40 and 76 years. The diagnosis was verified by clinical and laboratory examinations. The G-variant of MM was verified by immunofixation and electrophoresis. The definite diagnosis and disease staging was confirmed by a combination of diagnostic criteria. Heparinized blood samples were taken from the cubital vein in the morning (8 to 9 hours), in fasting state upon admission, prior to the starting a pathogenetic therapy. Dynamic monitoring of patients was carried out over the period of their staying in hospital. All patients were staged according to Durie and Salmon (1975) (stages II, III). At each stage, we discerned two sub-groups: A, without renal disease, B, with renal impairment. The control group consisted of 125 healthy volunteers matched for age and sex with the main group. IL-2, IL-4, IL-8, TNFα, and IFNγ levels in sera of the patients and healthy individuals were determined by enzyme immunoassay kits (JSC “Vector-Best”,Novosibirsk). In the myeloma patients, we have revealed an imbalance between pro-inflammatory (IL-2, IL-8, TNFα, IFNγ), and antiinflammatory cytokines (IL-4), with a predominance of pro-inflammatory factors. This finding does not exclude their potential pathogenetic role in growth and stimulation of tumor progression, and occurrence of infectious complications at any stage of the disease. The disturbances in cytokine regulation in MM patients may manifest as a deviation of cellular immune response by Th-1 way. As seen from our data, TNFα, IL-2 and IL-4 are the most significant cytokines for MM progression.

Toll-like receptors (TLR) are involved into innate immune recognition of microorganisms, including pathogenic bacteria. The aim of this work is to assess relative levels of TLR2 and TLR9 expression in cervical epithelial cells of women with inflammatory diseases of pelvic organs. The total group of patients consisted of 47 persons, including 20 women with urogenital infections, and 27 women comprised a control group. Using real-time PCR, we identified the opportunistic pathogens and gene expression levels of TLR2, TLR9 in the cervix epithelial cells. It was shown that expression of TLR9 in the group with urogenital infections was 13.7-fold higher than in control group. We have revealed that a significant increase of TLR9 expression in the mucosal epithelium from cervical canal correlated with detection of infectious pathogens in the samples. 

According to the WHO data, tuberculosis still represents a serious public health problem worldwide. Deterioration of socio-economic conditions in the population complicates epidemic situation for tuberculosis inRussia, thus leading to increase in acute progressive and complicated forms of tuberculosis in children and, consequently, to worsening structure of its clinical forms. Objectives: to determine associations between certain HLA-DRB1 alleles and risk of tuberculosis development in children. We examined 188 children aged from 3 to 14 years with various manifestations of tuberculous infection. Along with thorough examination of the patients, including multi-spiral CT scans of chest, we undertook genotyping of HLA-DRB1 alleles. Activity of tuberculous infection was determined by a set of immunological tests, i.e., tuberculin skin test, DIASKINTEST® (recombinant allergen of tuberculosis DIASKINTEST®). X ray diagnostics was performed with multi-spiral «Aquilion-32» computed tomograph (Toshiba), according to standard procedures. Molecular genetic typing of HLA-DRB1 alleles was performed by polymerase chain reaction (PCR-SSP), using standard commercial kits PROTRANS Ceclerplate System Protrans HLA-DRB1*. The children were divided into two groups: I group, 90 healthy children, II group, 98 children with tuberculosis. A comparisons group consisted of healthy donors (n = 346). Statistical processing of genetic material included evauation and analysis of the following parameters: frequency distribution of the antigen (F), χ2 criterion for significance (chi-square), the relative risk ratio (RR), etiologic fraction (EF), preventive fraction (PF). Children of the II group had significantly higher *04 allele HLADRB1*, as compared with control group (36.7% vs. 21.1%, χ2 = 10.08; р < 0.01). This finding may suppose a predisposal of these allele carriers to development of tuberculosis. At the same time, the rates of *07 (14.3% vs. 27.5%, χ2 = 7.15, р < 0.01) and *15 (18.4% vs. 28.3%, χ2 = 3.92; р < 0.01) HLA-DRB1* alleles were significantly lower, thus suggesting a protective effect of this allele. *04 allele seems to be a predisposing factor, whereas *07 and *15 alleles are protective for development of tuberculosis in children. 

Urban ecological problems are associated with industrial pollution emissions, waste of metallurgical production, unhealthy lifestyle and reproductive behavior lead to a steady rise in cancer pathology in theChelyabinskregion. Women in early reproductive age living in areas of ecological concern with suspected mastopathies, exhibit significantly higher levels of tumor markers associated with the tumor cell membranes of (CA19-9, SA15-5, CA125), CEA (carcinoembryonic antigen). Therefore, it seems necessary to perform massive laboratory programs for oncological screening, especially, among young working population, in order to identify breast diseases, and to arrange appropriate risk groups at this basis, aiming for development of effective preventive measures for the future. 

We studied blood contents of alpha-2-macroglobulin (α2-MG), pregnancy-associated alpha2-glycoprotein (PAG), and their immune complexes with IgG in healthy female controls, as well as in women with adenomyosis, females with uterine myoma (with or without proliferation), and in cases of a leiomyoma combined with adenomyosis. We found that the most pronounced reduction in α2-MG concentrations was observed in leiomyoma, but they were not decreased in a combination of myoma/ adenomyosis. The PAG levels, a known proliferation marker, have been shown to be increased only in the combined disorder. The amounts of immune complexes (α2-MG/IgG and PAG-IgG) were more significantly increased in leiomyoma complicated by adenomyosis. Correlative interrelationships between the studied parameters differed between normal and pathological conditions. Given that α2-MG and PAG are immunoregulatory proteins being actively involved in proliferative and inflammatory processes, we may assume that they participate in pathogenesis of immune-related uterine diseases, and, especially, in combined disorders.