Molecular mass of SCPB1 was estimated to be equal to 43.0±0.5 kDa. Immunization experiments were performed in laboratory animals to investigate the SCPB1 immunogenic properties. Maximum titers of IgG antibodies against SCPB1 (1:5,1 х 104 и 1:1,6× x 106 for mice and rabbits, respectively) indicated to SCPB1 immunogenicity. Moreover, the antibodies against SCPB1 were revealed in sera from women infected with GBS thus designating the humoral immune response of human organism to C5a peptidase fragment under study. Protective properties of anti-SCPB1 antibodies against were demonstrated by experiments in vitro (opsonophagocytosis), and in vivo (a model of GBS infection in mice).

Immunomodulating ability of a bacterial preparation (Immunovak VP-4 vaccine), and a compound of eukariotic origin (profetal), the main active component of human α-fetoprotein were under investigation in present study. Culturing of mononuclear leukocytes with the immunomodulatory factors promotes quantitative increase of the cells that express surface antigens specific for cytotoxic lymphocytes, natural killers and natural killer T-cells. Both bio-active preparations possess an expressed anti-cancer effect in vitro, i.e., they induce activation of killing properties of human peripheral blood mononuclear leukocytes, which is accompanied by acquiring their characteristic phenotype.

In spite of extreme controversies on possible role of cytokines as regulating factors in cancer pathology, their role during carcinogenesis is beyond doubts. Since regulation of cytokine gene expression is known to proceed, mainly, at the level of transcription, from promoter region, we have undertaken an analysis of genotypic frequencies in promoter regions of IL-4, IL-6 and IL-10 genes for a group of relatively healthy women and patients with breast cancer. Some specific features of allelic distribution have been found in groups of healthy women, among cohorts with hereditary predisposition, including the patients with breast cancer who had clustering of the disease in families (i.e., mother, grandmother, or sister been affected).

The patients with gastrointestinal cancer exhibit high contents of TNFα, IL-1β, IL-2, IL-6, IL-8, IFNγ, IL-1Ra and increased levels of anti-IFNα antibodies. Significant correlations are detected between histopathological parameters of the tumors, and the levels of TNFα, IL-2, IL-6, IL-8, IFNα, IFNγ, as well as antibodies against TNFα и IFNα. Moreover, we have determined diagnostically significant levels of cytokines and their combinations. On the basis of estimated diagnostic values, one may evaluate both current status of the tumor, as well as its potential malignancy grade.

Evaluation of proliferative and IL-2-producing activity of peripheral blood lymphocytes was
performed, using cultural methods, in patients with drug-sensitive and drug-resistant infiltrative pulmonary tuberculosis. The cell testing was performed at basal level and following in vitro stimulation with recombinant IL-2 and M. tuberculosis antigens. It was established that clinical course of infiltrative pulmonary tuberculosis, independently on drug sensitivity/resistance of the infectious pathogen, is accompanied by suppression of spontaneous lymphoproliferation. The levels of induced IL-2 production in drug-sensitive tuberculosis proved to be increased, whereas a reserve of IL-2-secreting reactivity of blood lymphocytes was lower than in drugresistant infection. Also, it was revealed that the level of lymphoproliferative response induced by IL-2, does not depend on clinical variant of tuberculosis, whereas stimulation of IL-2 production in blood lymphocytes is attained only in cases of drug-resistant tuberculosis variant.

A sufficient increase of infectious complications rate during early posttransplant period in allogeneic bone marrow (allo-BM) recipients has been traditionally explained by the prominent drop of serum IgG levels in the patients. That was the main reason for therapeutic application of intravenous human immunoglobulins in allo-BM-recipients. In present study, multiple repeated measurements of different IgG subclasses were performed in blood serum of thirty-six patients at early terms after allogenic bone marrow transplantation period, along with analysis of individual clinical data. The study revealed several factors that show significant associations with IgG levels posttransplant. Moderate decrease in concentrations of IgG subclasses was registered after conditioning treatment carried out before the transplantation. Significantly decreased concentrations of IgG subclasses have been revealed during bleedings, diarrhea and glucocorticosteroid therapy. In general, however, no regular prolonged deficiency for total IgG subclasses was found in allogeneic bone marrow recipients during early posttransplant period.

Abstract. We have evaluated effects of combined anti-hypertensive therapy upon the indexes of proinflammatory cytokines and clinical aspects of chronic heart failure among the patients suffering from essential hypertension (stages II-III, high and very high risk groups). The first group (n = 45) was treated with Enalapril + Hydrochlorothiazide, while the second group (n = 41) received Enalapril + Indapamide. Before starting the therapy, a pro-inflammatory cytokinemia was revealed, followed by a significant decrease of IL-6 and TNFαα levels in patients of the first group (p < 0,01), after two weeks of hospital treatment. During combined therapy, showed a sufficient decrease in systolic, diastolic and mean blood pressure levels for the both groups. A more pronounced regression of the mean blood pressure level was detected under Enalapril + Hydrochlorothiazide treatment (p < 0.002), accompanied by clinical improvement of chronic heart failure according to the clinical conditions rating scale (p < 0,001). Due to the correction of the systolic blood pressure level, all the patients showed a
decrease in fatal risk of cardiovascular complications: they have left a high-risk group (5 to 10% SCORE) for a low risk group (< 5 % SCORE).

Abstract. A study was carried out in hundred-five patients with severe or mid-severe clinical course
of community-acquired pneumonia. Clinical observations showed that introduction of Imunofan and
Polyoxidonium within combined therapeutic regimen administered to the patients, exerts a pronounced positive effect upon clinical course of disease and normalization of immune characteristics. Due to immunocorrective treatment with Imunofan and Polyoxidonium, the patients with community-acquired pneumonia, exhibited a distinct trend to earlier normalization of both cellular and humoral immunity indexes. This result provides further proofs for efficient treatment with immunomodulatory drugs, e.c., by means of Imunofan and Polyoxidonium.

Abstract. A new role of B-cells in pathogenesis of multiple sclerosis (MS), their relations with B-cells in
development of inflammation and probable mechanisms of advanced therapeutic intervention in order to reach B-cell depletion are subject to discussion in present article. Here we describe a clinical case of MS with a resistant clinical course, and results of anti B-cell treatment. To attain maximal clinical effect, a novel therapeutic regimen (a combination of rituximab and mitozantrone) was applied. Clinical, radiological and laboratory methods were used to substantiate the efficiency of treatment.

Abstract. In this study, we evaluated effects of statins and other biological preparations upon spontaneous and stimulated activation of МАРК p38 and ERK1/2 in monocytes from the patients with rheumatoid arthritis (RA). We used peripheral blood mononuclear cells (PBMC) from RA patients and healthy donors. PBMC were cultured in presence of 0, 0.1, 1 or 10 мM mevastatin, 10 мg/ml IL-1 receptor antagonist (IL-1Ra), 5 мg/ml infliximab, and 5 мg/ml soluble pegylated p55 TNF-receptor (r-met-Hu-sTNF-RI). To study the mechanisms of mevastatin effects upon МАРК p38 and ERK1/2 activities, L-mevalonate was added to the cultures. The cells were stained with anti-phospho-MAPK p38, or anti-phospho-ERK1/2, and analyzed with flow cytometry. We have shown that IL-1Ra and r-met-Hu-sTNF-RI inhibited spontaneous MAPK р38 activation. Mevastatin reduced spontaneous MAPK p38 and ERK1/2 phosphorylation. Mevastatininduced suppression of MAPK p38 and ERK1/2 activation was not dose-dependent. L-mevalonate completely prevented mevastatin-induced reduction of MAPK р38 phosphorylation and partially reversed inhibition of МАРК ERK1/2. In conclusion, decrease in MAPK activation represents a common mechanism of anti-inflammatory effects exerted by statins and some other biologicals.

Abstract. While employing an enzyme linked immunosorbent assay, it was shown that UV-sensitivity is different for various adhesion molecules (CD2, CD11a and CD29) at the membranes of T-lymphocytes. Relative photoresistance of CD2 and CD11a antigens to UV irradiation was established at the doses range of 151 to 906 J/m2, a large dose of UV-iradiation (1359 J/m2) exerted a suppressive effect upon their expression level. An immunomodulatory action of UV-radiation was revealed upon expression of CD29 transmembrane protein by T-cells. A dependence between amino acid structure and photosensitivity of CD2, CD11a and CD29 antigens of T lymphocytes is analyzed and discussed.

Abstract. During attacks of familial mediterranean fever (FMF), multiple systemic events are triggered, most of which promote autoinflammatory reactions. A molecular pattern of immune abnormalities in FMF is yet unclear. There is an increasing evidence to suggest an involvement of the complement system, the major inflammatory mediator, in FMF pathogeneses. In present study, we examined functional activities of the alternative and the classical complement cascades, and some relationships between alterations in the functional activities of these cascades in FMF. To this purpose, we measured hemolytic activities of classic (CH50) and alternative complement pathways (AH50), and of the complement components C3 (C3H50), factor B (fBH50) and factor D (fDH50) in blood serum of twenty-eight colchicine-free FMF patients and twenty-five healthy subjects. According to the data obtained, a decrease in serum levels of AH50 and increase in CH50 and C3H50 were detected in FMF patients, as compared to normal values. No significant difference was detected between the affected persons and healthy subjects for fBH50 and fDH50. Correlation analysis revealed a positive relationship between alterations in CH50 and C3H50 and a negative correlation between alterations in AH50 and CH50. From the data obtained, following conclusions have been made: 1) pathogenesis of FMF is characterized by a complement dysfunction, including hyperactivation of classical complement pathway and hypoactivation state of alternative pathway; 2) alterations in functional activities of classical and alternative complement activation pathways in FMF are interdependent; 3) the alternative pathway is suppressed on the initial stage of its activation; 4) high blood levels of C-reactive protein, serum amyloid P component, and circulating immune complexes, associated with FMF, might be responsible for hyperactivation of classical complement pathway in this disease.

Abstract. Using modern immunological methods of studies, we investigated some immunopathogenetic aspects of rheumatoid arthritis complicated by chronic herpesvirus infection. It was established that both rheumatoid arthritis, and chronic herpesvirus infection are accompanied by pronounced imbalance in production of immunoregulatory Th1/Th2-cytokines produced in immunocompetent cells of peripheral blood. In case of rheumatoid arthritis combined with herpes simplex infection, IL-2 and IFNγγ levels were decreased, whereas IL-4 и IL-6 levels proved to be increased, as compared with isolated diseases under study.

Abstract. The aim of the work was to evaluate clinical features of purulent wounds trend and functional activity of local wound phagocytes in the patients with odontogenic phlegmones in the course of local treatment with Ronkoleukin. A randomized clinical study was performed which included sixty-five patients with odontogenic phlegmones. Their age ranged from 18 to 74 years old. The group was divided in two parts, i.e., patients of a comparison group (n = 33) receiving a conventional combined drug therapy, and the persons from study group (n = 32) who were subject to local immunotherapy with Ronkoleukin, applied along with conventional therapy. It was established that the local therapy with Ronkoleikin exerts distinct positive effects, i.e., increase in wound-located lymphocytes and macrophages, acceleration of phasic dynamics of inflammatory events, augmentation of an lysosomal luminescence index (2.3-fold), enhancement of phagocytosis intensity in wound neutrophiles and macrophages (1.9-2-fold), strengthening the reserve abilities of wound neutrophils (1.3-fold). These effects create favorable conditions for elimination of pathogen and optimal healing of purulent wounds in the patients with odontogenic phlegmones.

Immunomodulatory activity of a native antimicrobial peptide indolicidin and its synthetic structural analogues (indolicidin 7, 8,20,21,22), with spatial uncoupling of hydrophobic and hydrophilic parts of the molecule and different net charges was under investigation. It was revealed that indolicidin 7 and 22 at concentrations of, respectively, 0.6 uM and 5 uM suppressed cytotoxic activity of natural killer spleen cells against tumor cells (K-562 line), while indolicidins 8,20 and 21 at the concentrations of 1.3 uM, 2.5 uM and 5 uM respectively, did not influence it. It was shown for the first time, that native indolicidin and its structural analogues indolicidin 8 and 20 did not increase activity of cell division, whereas indolicidin 7 and 22 had a direct mitogenic activity on spleen cells. The investigated peptides showed inhibitory effect upon mitogenic transformation of splenocytes induced by Con A. In addition, indolicidin and its structural analogues suppressed co-mitogenic activity of Interleikin-1 towards splenocytes. The results obtained allow of a conclusion that the structural changes of indolicidin molecule lead to emergence of novel immunomodulatory activities of the peptides, whereas the methods of structural modifications demonstrate potential approaches to directed design of molecules with optimal biological properties.