Despite of considerable differences in etiology, pathogenesis, clinical and laboratory, data, and, finally, different clinical features of such diseases as atherosclerosis, autoimmune and allergic diseases, there exists a lot of evidence suggesting that, basically, these disorders have much in common. First of all, it concerns epigenetic regulatory mechanisms of gene expression that show virtually identical patterns of changes, i.e., total hypomethylation and reversible hypermethylation of distinct genes. The events connected with regulation of telomere length are also similar in all the mentioned disorders. In general, this concept draws attention to current needs for urgent development of novel therapeutic approaches for these very common disorders, by means of drugs that would be able to influence some molecular mechanisms, underlying epigenetic regulation of gene expression.

We studied the effect of a recombinant murine TNF (rmTNF) and TNF-binding protein of Variola virus (VARV-CrmB) upon colony-forming ability of bone marrow cells (BMC) from Balb/c mice. BMC were grown in semisolid methylcellulose medium supplemented with murine growth factors in the absence or presence of mrTNF along at concentrations ranging from 2 to 40 ng/ml, VARV-CrmB (2 to 24 ng/ml), as well as in presence of both mrTNF (2 ng/ml) and VARV-CrmB (2 to 12 ng/ml). Hematopoietic colonies (BFU-E, CFU-E, and CFU-GM) were scored on day 14. VARV-CrmB protein didn't influence clonogenicity of the bone marrow progenitors. rmTNF inhibited growth of erythroid cells (BFU-E+CFU-E) at all concentrations tested, and stimulated growth of granulocyte-macrophage progenitors (CFU-GM) at concentrations of 2 ng/ml and 10 ng/ml. Combined effect of rmTNF and VARV-CrmB resulted into abolition of rmTNF-induced reduction of BFU-E+CFU-E formation and rmTNF-induced increase of CFU-GM number up to basic levels. Thеse results clearly demonstrate the anti-TNF activity of recombinant viral VARV-CrmB protein.

The article presents experimental data on regulatory effect of neutrophilokine helper fractions on the macrophage (Mph) functional activity in the course of antiplague immunity formation. It has revealed that these fractions content biologically active, low-molecular weight peptides. They stimulate Mph killing activity by increasing phagosome-lysosome fusion, thus boosting transformation of monocytes to Mph, and causing redistribution of macrophage subpopulations in the total cellular pool. The helper effect of neutrophilokine fractions upon functional activity of MPh is more pronounced during secondary immune response.

The relationship between various subpopulations of regulatory T-cells (Treg) and serum level of CA-125 and dynamics of Treg following surgery in ovarian cancer (OC) patients have been investigated. The typical for OC peripheral blood Treg changes (the enchantment of CD4+FoxP3+ и CD8+FoxP3+ T-cells and decrease of CD4+CD25+/CD4+CD25high Т-cells due to their migration to ascites) have been revealed only in patients with elevated CA-125 level and were not registered in patient's group with normal level of this antigen. CA-125 serum level was directly correlated to absolute count of CD4+CD25high Т-cells and was in reverse relation to CD8+FoxP3+ T-cells. Surgical removal of a tumor was accompanied by remarkable reduction of CA-125 level in all cases. However Treg changes were observed only in patients with optimal cytoreductive surgery and were evidenced by CD4+CD25+/CD4+CD25high Т-cell normalization, whereas the number of these cells in peripheral blood of patients with residual tumors after surgery remained decreased. At that percentage of CD4+FoxP3+ и CD8+FoxP3+ Т-cells 2 weeks after surgery was unchanged and their increased number was associated with persisted decrease of T-cell proliferation in response to anti-CD3 stimulation.

Characteristics of CD34+ cells mobilization were studied in children suffering with various diseases, like as their dependence on type and extent of inflammatory response. It was revealed that the children with signs of systemic inflammatory response syndrome exhibit a significant increase of absolute content and percentage of circulating CD34+ cells, whereas children with frequent infections, and with clinical signs of allergy during recurrence of their chronic allergic disease showed a significant decrease in CD34+ cell percentage. Meanwhile, children with allergoses, and those with common recurrent infectious states did not reveal any deviations in CD34+ cells from normal values.

Subpopulation indices of peripheral blood and pleural exudate lymphocytes have been studied in the patients with various clinical variants of a tuberculous pleurisy. It has been shown that, in patients with both MBT-negative and MBT-positive variants of tubercular pleurisy, decreased quantity of CD3- and CD4-positive lymphocytes was observed, whereas an increase in numbers of CD8+ and CD16+ lymphocytes was more pronounced in the persons with MBT-negative pleurisy. In pleural exudates from the patients with tubercular pleurisy, the numbers of CD3+ lymphocytes proved to be significantly higher than their contents in peripheral blood. It may be assumed that lymphocytosis in pleural exudates results from migration of the cells from peripheral blood into pleural cavity. It is revealed that, during exudative pleurisy of tuberculosis origin, T-cells with CD4+ and CD8+ phenotype are more likely subject to migration into pleural cavity, accomplished by additional migration of CD16+ lymphocytes in MBT-positive cases of pleurisy.

Evaluation of lymphocyte subsets in severe forms of herpetic infection is a necessary diagnostic test. However, interpretation of appropriate data is difficult, due to slight or multidirectional changes of immunological parameters in the patients. In present study, the indices of immune status were assessed in the patients with severe recurrent forms of chronic herpetic infection, being in remission period by the time of study. A detailed personalized analysis of immunological testing data is presented, with respect to the disease duration, recurrence frequency, and other clinical features of severe herpes infection. Various types of correlations between the lymphocyte subpopulations are described for the patients with severe recurrent herpetic infection.

Peripheral blood monocytes play a key role in regulation of immune response during pregnancy. Intensive adhesion of monocytes to endothelium proves that monocytes are activated during pregnancy. To determine a potential role of adhesion molecules for ability of monocytes to adhere, we studied expression of CD11a, CD11b, CD11c, CD18, CD49d, CD29 markers of monocytes from non-pregnant and pregnant women. Expression of adhesion molecules on monocytes was analyzed by flow cytometry. The amounts of CD11b-expressing monocytes increased during pregnancy, as compared with non-pregnant women. Intensity of CD11a, CD11b, CD11c, CD29 expression on the monocytes did also increase at normal pregnancy. These results suggest that intense adhesion of monocytes to endothelium during uncomplicated pregnancy may be determined by increased expression of CD11a, CD11b, CD11c, CD29, and higher amounts of CD11b+ monocytes.

The paper presents comparative data concerning immunoglobulin E balance, as well as IL-4 and IFNγ amounts, in the patients with chronic nephritis with a favorable outcome vs. therapy failure after a standardized treatment. Results of treatment applied were evaluated by expert conclusions of the doctors, according to analysis of clinical and laboratory data. It has been shown that initial levels of IL-4 prior to the beginning of therapy were increased in the patients with inadequate response to therapy, as compared to healthy persons. Moreover, the patients with inadequate response to the treatment exhibited an increase in IgE concentrations and altered cytokine balance, thus suggesting a differentiation shift from naive Th to Th2 type, accompanied by development of allergic inflammation.

Chronic obstructive pulmonary disease (COPD) is associated with pulmonary and systemic inflammation. The latter is likely to contribute significantly to the pathobiology of numerous extrapulmonary effects of the disease, i.e., systemic effects of COPD. The main causes of systemic inflammation in COPD remain to be elucidated. A course of local vs. systemic inflammation is determined by an imbalance between pro- and anti-inflammatory cytokines. Cytokines are fundamental to regulation of the inflammatory process developing in response to an injury. Certain shifts in their homeostasis may lead to a local or systemic disorder. We compared relative contents of pro- and anti-inflammatory cytokines, along with TGF-β levels in bronchoalveolar lavage (BALF) and blood sera from the patients with stable moderate and severe COPD. It has been shown that increased levels of pro-inflammatory mediators were not counterbalanced by an appropriate up-regulation of anti-inflammatory cytokines, both in BALF and peripheral blood of COPD patients, thus causing their altered interrelations. Comparison of levels of these cytokines in BALF and serum did not reveal any direct correlations, thus suggesting that systemic inflammation is not due to mere overflow of inflammatory mediators from the pulmonary tissue, while assuming some other mechanisms that may determine evolvement of this disorder.

Fifty-four patients with different clinical course (acute and protracted forms) of community-acquired pneumonia (CAP), were studied for interleukin-8 (IL-8) contents in blood serum and its production levels (spontaneous and PHA-stimulated), depending on the IL-8 gene polymorphism at the 251 T → A locus. Employing the data about immunogenetic differences, we have shown some associations between IL-8 production, depending on clinical outcome (adequate responders vs poor response to medication in acute pneumonia). Both in acute and chronic forms of pneumonia, poor response to therapy was associated with decreased reserve capacity of IL-8 production, and a downward trend of cytokine concentration in blood serum. It was revealed that the CAP patients with poor response to treatment exhibit deficient production of IL-8 associated with homozygous AA genotype at the -251 T/A locus of IL-8 gene.

The article contains results concerning combination frequency analysis for a wide number of three- to six-locus constellations of cytokine gene alleles, i.e., IL-1B T-31C, IL-6 G-174C, TNFA G-238A, TNFA G-308A, TNFA C-863A, IL-4 C-590T, IL-10 C-592A. The study was performed in a group of 104 patients with rheumatoid arthritis (RA) who were subject to basic therapy with methotrexate. An association was found between certain individual multi-locus allele combinations, and efficiency of the therapy, as defined by decrease in DAS28 index following 24 week of methotrexate treatment. An association was demonstrated between adverse effects of drugs used, and a "cytokine genotype" of the patients. Analysis of the results was carried out with respect to correlations between the levels of pro- and anti-inflammatory cytokine production and promoter polymorphisms of respective genes. We assume that further clinical research will allow to use our results as pharmacogenetic criteria in order to choose more effective personalized therapies, taking into account the genotypes of RA patients.

Levels of IgM autoantibodies (AAbs) to native (double-stranded) and denaturated (single-stranded) DNA were studied in blood serum of sixty patients with hemorrhagic fever with renal syndrome (HFRS) and twenty-five healthy persons, using an ELISA technique. The median levels of IgM AAbs to double-stranded DNA in blood serum of healthy persons and HFRS patients corresponded to 0.41 and 0.53 arbitrary units, respectively. Thus, the difference between the samples from HFRS and healthy persons proved to be non-significant. The median level of IgM AAbs to single-stranded DNA in blood sera of HFRS patients (0.71 arbitrary units) did significantly exceed serum values of healthy persons (0.57 arbitrary units). A probable involvement of IgM AAbs into regulation of IgG AAbs' production during virus-induced activation of autoimmune events in HFRS patients is discussed.

In the children with secondary infective endocarditis, the contents of TNK cells was found to be decreased. Same patients exhibit low concentrations of total IgG and its subclasses, IgG1 and IgG2 subclasses decreased, whereas IgG4 levels are increased. Stimulated phagocytic response is also decreased in these patients, along with increased numbers of lymphocyte/platelet cell aggregates. Effect of a conventional treatment with addition of thymalin when treating secondary infective endocarditis, was more pronounced, in comparison with conventional therapy, with respect to restoration of humoral immunity, phagocytic activity of leukocytes and lymphocyte-platelet adhesion.

Uterine cervical cancer is among the main items of modern oncology. Determination of SCCA levels in blood serum of women with locally disseminated forms of uterine cervical cancer has a great significance for estimation the extent of lesions, tumor progression patterns, as well as treatment monitoring. During our study, we have determined that, before starting a specific treatment, all the patients with locally disseminated forms of cervical cancer had high serum levels of SCCA, along with suppressed anti-tumor immunity.Interestingly, high SCCA levels in blood serum proved to correlate with a decrease in anti-tumor immunity factors in those patients who showed a negative dynamics of tumor progression within one year after the therapy was performed. Meanwhile, the patients with positive post-treatment dynamics exhibited a significant decrease of SCCA levels over a year after therapy, as compared with appropriate pre-treatment values, accompanied by increase in anti-tumor immunity markers in these cases.

The aim of present study was to determine the microbial pattern and a significance of local pustular immune factors for the progression of local pyogenic infection in surgical patients. To these purpose, specific infectious pathogens were identified and scored by means of conventional microbiological methods in the patients with pyogenic inflammatory diseases of skin and subcutaneous fat tissues. The numbers of purulent leukocytes were determined in the pustular exudates, and concentrations of TNFα, IL-1β, IL-8, IFN-γ, IL-4, IL-1ra, IgM, IgG, and IgA were measured in the samples, using enzyme immunoassay techniques. Appropriate parameters of effluents obtained from "clean" (non-infected) surgical lesions were taken as сontrols. It has been shown that Staphylococcus aureus plays a leading role in etiology of bacterial infections in our patients. The amounts of blood cells in pustular samples showed a direct and significant correlation with number of viable microorganisms derived from the effluent. Purulent wound exudates were characterized by high IL-1β and IL-8 concentrations, along with relatively low TNFα levels, as compared with "clean" wounds. Mean amounts of IgG in the pustular contents of dissected lesions proved to be five-fold higher that IgG levels in sterile incisions. As compared with young individuals, the elderly persons are characterized by lesser TNFα production, as well as by more active IL-8 synthesis in the areas of bacterial inflammation. The indexes of local immunity show sufficient differences between the areas of suppurative inflammation and sterile wound lesions.

The study was focused on identification of disorders in immune homeostasis in the mucosalivary area, using cytofluorometric analysis of immune cell populations and quantitative enzyme immunoassay for interleukin-17 in saliva of radiochemical facility workers with a history of smoking, being at initial stages of chronic obstructive pulmonary diseases (COPD) without exacerbations. We have observed a cohort of COPD patients (144 workers), as well as a group of 264 smoking individuals without any signs of COPD. The study and control groups have been matched by age, gender, working conditions, smoking index and clinical history. During the last ten years, the persons under study were subject to a regular follow-up. The current study included twenty-three patients from the main group and ten individuals from the group of comparison. Analysis of immunocytes in saliva was peformed by means of flow cytometry. The patients for laboratory studies were selected in a random manner. Total amounts of leukocytes was measured in saliva, providing a mean value of 2.4106/ml, followed by filtration of saliva through porous filters (Becton Dickinson). Cytofluorimetric analysis was performed be means of BD FACSCanto II machine, using a kit of appropriate monoclonal antibodies, thus allowing of a four-colour fluorescence analysis. The salivary immune cell subpopulations were scored with viable cells, positive for CD4+. A significant increase in amounts of CD+CD8- (25.85% versus 1.4% in the control group, p = 0.049) and in CD+CD+ (3.3% versus 0.6%, p = 0.049) was noted in COPD patients, hence presuming an increase in total amounts of T-lymphocytes and T-helpers, without any enhancement of cytotoxic cell populations in the mucosalivary region, being permanently exposed to tobacco smoke in the smokers with COPD. The obtained findings let us to assume an involvement of CD+CD+ lymphocytes in pathogenesis of inflammatory alterations at COPD. An increased level of IL-17 was revealed in COPD patients group, versus those smokers, who had no clinical signs of COPD, thus suggesting activation of secretory functions in a subpopulation of CD+CD+ lymphocytes (i.e., Th17).

Influence of lipopolysaccharide (LPS) composition upon activation of human blood mononuclears was investigated, by measuring levels of pro-inflammatory TNFα and IL-6 cytokines released by the cells. It is shown that LPS from Rhodobacter capsulatus PG, in contrast to E. coli LPS, did not activate the target cells for synthesis of the cytokines.

Human papillomaviruses (HPV) infection are considered as a triggering factor of cervical neoplastic events (e.g., CIN) and are responsible for many cutaneous and mucosal lesions of cervix uteri. CIN commonly emerges from benign cervical tissue changes. There is clear evidence that local immune response in reproductive system plays a major role in the control and course of benign cervical tissue changes. Neutrophils play main role in encountering pathogens, primary antigen reactions and mediate powerful inflammatory effects. They are involved into development of antitumor response. The main purpose of our investigation was to study some indexes of neutrophil functional activity in women with CIN II-III associated with HPV-infection. It was shown that considerable changes in functional activity of neutrophils in mucous cervical secretions from women with CIN II-III, as compared to patients with chronic inflammation, accompanied by benign cervical changes (cervical ectopia). The alterations of neutrophil functional activity in women with CIN II-III may sustain a local chronic inflammation, associated with HPV-infection, thus increasing probability and predicting a of higher-grade tumor disease.

Effects of a 12-week acceleration exercise program (whole body vibration) were studied in 39 elderly women. Immune cell subsets, expression of lymphocyte activation markers, levels of pro-inflammatory serum cytokines (IL-8 and TNFα), and serum immunoglobulins (A, M, G) were evaluated. It has been revealed that the progression-based acceleration training is not a sufficient stress factor affecting immune functions, and it does not produce any significant postexercise suppression of immune functions in elderly women.

The study aimed to compare subset composition of peripheral blood lymphocytes in 40 newborns at different gestation periods, complicated by a verified prenatal infection (1st group), or with hypoxic brain damage (2nd group), using a flow cytometry technique. It was found that activated CD14+HLA-DR+ monocytes were 2,3-fold more common in the infants from the 1st group, and representation of CD5+CD19+ B1 lymphocytes (a «forbidden» clone) was 1,8-fold higher than in 2nd group. Among pre-term babies from the 1st group, the lymphocytes with CD3+CD16+/CD56+, CD3+CD95+ and CD5+CD19+ phenotype were registered more often, than in full-term infants (resp., 5, 11, and 2 times higher). These data argue for involvement of compensatory defense immune mechanisms under the conditions of increased antigenic load, being more pronounced in pre-term infants.

 Examination of the patients with chronic generalized periodontitis revealed a sufficient increase in all immunoglobulin classes, i.e., IgG, IgM, IgA, sIgA, as well as increased IL-8 concentration in their salivary samples. Emergence of antibodies to heat-shock proteins suggests a pathogenetic role of chaperon-like proteins in development of periodontal diseases.

We have performed immunophenotyping of lymphocytes in 150 HIV-positive patients, by means of flow cytometry. All the persons under study were classified into three groups, depending on absolute contents of CD3+CD4+T-lymphocytes in peripheral blood, according to HIV infection staging in adults and adolescents, as amended by CDC (USA). It was revealed that, at each subsequent stage of disease, a decrease in absolute numbers of T-helpers is accompanied by drop in relative and absolute numbers of lymphocytes, as well as in total T-lymphocyte numbers, and decreased amounts of absolute cytotoxic T-lymphocytes levels, combined with increase in their relative contents, along with decreased CD3+CD4+/CD3+CD8+ ratio, diminished levels of double-positive subpopulation, decrease in relative and absolute levels of αβТ-lymphocytes and significant drop in absolute levels of γδТ-cells, while their relative amounts remained normal. These findings demonstrate a pattern typical to the absence of immunological reactions in response to antigens persisting in the organism.

 Inflammatory markers and activity of lymphocyte-to-platelet adherence (LTA) have been studied in fifty-eight patients with osteoarthritis. Sixteen healthy individuals were included in the control group. Changed production of inflammatory cytokines, i.e. an increased concentration of pro-inflammatory cytokines (IL-1β, TNFα, IL-6), and increased activity of LTA have been observed in patients with osteoarthritis, as compared to the control group data. A correlation was found between the levels of inflammatory cytokine production, and activity of lymphocyte-to-platelet adherence.

Present work deals with specific immunologic changes that are typical to various types of mixed infection caused by viruses from Herpesviridae family during their activation phase. These changes include increased amounts of CD3+/CD25+ lymphocytes and CD3+/CD4+ cells, decreased levels of CD3+/CD95+ cells, increased contents of natural killer cells, altered interrelations between the immune system parameters. Involvement of cytomegalovirus or Epstein-Barr virus (EBV) in the mixed infection is associated with some special changes of the lymphocyte subsets. I.e., a co-infection with herpes virus simplex (HSV) type 1/2 and cytomegalovirus is characterized by increased amounts of activated T-lymphocytes and T-helper cells, whereas mixed HSV/EBV infection is accompanied by sharp reduction in CD3+/CD95+ lymphocytes.

Studies of functional activity of neutrophilic granulocytes from patients with chronic rhinosinusitis was performed using luminol- or lucigenin-dependent chemiluminescence. We have revealed increased production of reactive oxygen species (ROS) both under basal conditions, and in zymozan-induced chemiluminescent reaction, employing luminol as an activator, and determining total functional activity of neutrophils. Meanwhile, in lucigenin-induced chemiluminescence associated with production of superoxide anion radicals, a delayed ROS production was revealed, both in spontaneous and zymozan-induced response. One may suggest that, when studying these pathological events in neutrophils, ROS production in the cells proceeds mostly by myeloperoxidase pathway.

We have measured total levels of alpha-2-macroglobulin (α2-MG), its immune complexes with IgG (α2-MG-IgG), along with IL-6, IL-8, IL-10, TNFα, lactoferrin (LF) and alpha-1-antitrypsin (AT) contents in blood sera of children with verified chronic adenoiditis (ChA), pharyngeal tonsil hypertrophy (PhTH), and in sera of healthy children. It was shown, that α2-MG, α2-MG-IgG, AT, IL-10 serum concentrations in ChA and PhTH were significantly increased in comparison with appropriate values in healthy children. Moreover, we have detected significant increase in LF, and slight decrease of IL-6 and IL-8 contents in sera of ChA patients. All general trends of detected changes were similar for both diseases, but some changes proved to be differently expressed. In ChA, however, we found higher levels of circulating α2-MG molecules in circulation, some deficiency in IL-6 and IL-8, and significant abundance of IL-10 and LF at the beginning of ChA, thus resulting into a chronic disorder. In PhTH patients, there was no such remarkable abundance of α2-MG and LF in circulation, and no deficiency in IL-6 and IL-8, but higher levels of damaged α2-MG molecules complexing with IgG, total α2-MG, AT and IL-10 excess may provoke distinct metabolic changes and compensatory proliferation of tissues in this disorder.

In present work, we studied cytokine levels and performed analysis of some immunologic parameters in the patients with chronic lymphocytic leukemia (CLL) before and after treatment with monoclonal anti-CD52 antibody (alemtuzumab). In comparison with a control group, the CLL patients before alemtuzumab treatment showed a significant decrease in relative contents of CD3+ and CD4+ lymphocytes, CD4+/CD8+ T cells, diminished IFNγ and IL-4 levels, and a trend for TNFα increase. After ceasing the alemtuzumab treatment, the patients with CLL exhibited a significant decrease in absolute amounts of mature T-lymphocytes, CD4+, CD8+, CD20+ cells, as well as decreased relative contents of CD16+ lymphocytes. A sufficient post-treatment drop of serum IL-2 concentrations and a trend for serum TNFα and IFNγ decrease were also observed, as compared with pre-treatment values. The changes revealed may be connected with an additional immunosuppressive effect of alemtuzumab. The dynamics of cytokine levels and immunological parameters associated with alemtuzumab treatment is indicative for a weakening of cell-mediated immunity, thus resulting into a potential risk of infectious complications.

Thymic gland was examined in three children with Mauriac syndrome, using ultrasonographic studies. Some novel results were obtained, concerning dimensions, echostructure and vascularization of thymus in this disorder. Absence of detectable age-related thymic involution in these patients is of special interest, thus, probably, reflecting an increased functional activity of thymus in complicated cases of type I childhood diabetes, e.g., in Mauriac syndrome.