Abstract. The effects of cholesterol (Ch) diet, i.p. administration of mevalonic acid (Mev) and their combined application upon nitric oxide (NO) production in peritoneal macrophages, as well as upon biochemical characteristics of kidney function derangements, and histological parameters of tissue alterations, infiltration and fibrosis were studied in experimental model of chronic rhabdomyolysis-induced renal injury induced in C57Bl/6 mice. The effects of Ch diet, Mev and their combination on the degree of renal fibrosis were also studied in a model of unilateral ureteral obstruction. In normal animals, and, especially, in nephrotic mice, Ch diet was shown to cause a dramatic decrease of LPS-induced NO production, whereas Mev did enhance NO production significantly. Administration of Mev during Ch treatment abolished, in part, the suppressive effect of Ch. Ch diet was shown to enhance fibrotic response, without significant effect upon tissue alteration and mononuclear infiltration, whereas Mev enhanced alterative component and slightly diminished fibrosis. We conclude that Ch diet and Mev exert opposite effects upon the course and outcome of chronic nephropathy for their inhibitory (Ch) and stimulating (Mev) effect on mevalonate pathway, which is involved in the control of macrophage M1-M2 polarization.

Abstract. Present study was performed to investigate the influence of polysaccharide fragment or lipid A upon induction of TNFα and IL-6 cytokines. The study was performed with human THP-1 monocytic leukemia cells that were induced to differentiate into macrophage-like cells using PMA treatment. Bacterial lipopolysaccharides from S. typhimurium (S-chemotype form), S. typhimurium SL1181 (R-chemotype, Re-mutant), E. coli O55:B5 (S-chemotype), and E. coli JM103 (R-chemotype, Re-mutant) were used in this study. A decreased molar ratio for lipid A-KDO in S-form of LPS from E. coli is accompanied by diminished TNFα and IL-6 expression. By the contrast, for S-form of LPS from Salmonella, a decrease in lipid A-KDO molar ratio did cause a sufficient enhancement of TNFα expression. A contribution of lipid A structure into biological activity of LPS is more significant for Re-chemotype than for S-chemotype, independently on bacterial species.

Abstract. Pogrammed cell death of peripheral blood mononuclear leucocytes from patients with acute inflammatory diseases (non-nosocomial pneumonia, acute appendicitis) was investigated under ex vivo conditions, upon cultivation of the cells with selective inhibitors of JNK (SP600125) and р38 МАРК (ML3403). In vitro addition of SP600125 and ML3403 under oxidative stress conditions prevents increase of annexinpositive mononuclear cells numbers, thus suggesting JNK and р38 МАР-kinases to be involved into oxidative mechanisms of apoptosis deregulation. A role of JNK in IL-8 production by mononuclear leucocytes was revealed in cases of acute inflammation. Regulatory effect of JNK and p38 MAP-kinases can be mediated through activation of redox-sensitive apoptogenic signal transduction systems, as well as due to changes in cellular cytokine-producing function.

Abstract. A significant telomere shortening was shown in both total peripheral lymphocyte populations and CD4+ T-cells from patients with bronchial asthma, as compared to normal donors. Such shortening takes place in different cell subpopulations depends on different types of bronchial asthma. In patients with intrinsic asthma, a telomere contraction was found both in CD4+ and CD8+T-lymphocytes, but only in CD4+ lymphocytes from patients with extrinsic-type asthma. We didn’t found any changes of telomere length in patients with mixed-type asthma, however, a significant correlation was found between telomere length in both CD4+ and CD8+T- cells, and serum IgE concentrations.

The data obtained demonstrate that telomere shortening in lymphocytes may take place not only due to T-cell exhaustion, or homeostatic proliferation induced by lymphopenia, but also due to expansion of antigenreacting cells. The entire data point to sufficient pathogenetic differences for various types of bronchial asthma. A non-uniform contribution of atopic and infectious inflammation may present an important reason for different patterns of the disease development.

Abstract. In spite of similar clinical patterns, there are numerous differences in immunopathogenesis of intrinsiс and extrinsiс forms of atopic dermatitis. Patients with both forms have decreased levels of CD8+CD25+ lymphocytes, decreased telomere DNA length of CD4+T-cells, decreased migration inhibition index in delayedtype hypersensitivity, decreased levels of CD16+NK-cells, decreased Fc-dependent monocyte and granulocyte phagocytosis, increased hydrogen peroxide production by neutrophils, increased levels of CD19+B-cells, as well as high IgA and IgG immunoglobulin levels. Extrinsiс form of atopic dermatitis are characterized by more severe clinical course, and by involvement of both immediate hypersensitivity (hyperproduction of IgE and decreased T-cells with intracellular IFNγ production), like as delayed-type hypersensitivity (decreased migration index along with decreased migration inhibition index). CD8+ play a large role in extrinsiс form of atopic dermatitis that may be traced as decreased telomere length of CD8+T- cells, decreased levels of CD8+CD45RO+ cells, increased levels of CD8+CD45RA+ naive cells and increased levels of CD28+ costimulatory molecules on CD8+cells. Increased levels of CD4+CD25+bright cells and strongly alterations of innate immunity determined of decreased H2O2 production by monocytes are shown in extrinsiс form. Hence, the severity index of atopic dermatitis is more expressed in extrinsic form of bronchial asthma and it is, probably, determined by more exaggerated immunological alterations.

Abstract. The present work was aimed to evaluation of phenotype and functional properties of IFNα-induced dendritic cells (DCs) in normal pregnancy, and in cases complicated with suprarenal hyperandrogenia (HA), as well as in vitro assessment of dehydroepiandrosterone sulfate (DHEAS) effects upon DC functions. As compared with non-pregnant women, DCs from healthy pregnant women are notable for impaired maturation/activation, whereas fractions of mature (CD83+) and activated (CD25+) cells DC were similar in normal pregnancy and in women with HA. Blood sera from healthy pregnant women inhibited generation of mature DCs, whereas sera of women with HA and direct supplementation with DHEAS enhanced maturation and activation of DCs. Functional analysis of DC capacity to stimulate Th1 (IFNγ) and Th2 (IL-4) cytokine expression in MLC has shown that, in contrast to non-pregnant women with T1-cell activation by DCs, the DCs from healthy pregnant women caused predominant activation of CD3+IL-4+Т-cells. In HA-complicated pregnancy, DCs were capable to stimulate both Th1- and Th2-cytokine production in T-cell populations. Meanwhile, addition of DHEAS to DCs cultures were accompanied by enhancement of their T1- polarizing activity. DCs from women with normal pregnancy exerted inhibitory effect upon activated NK-cells that was evidenced by a relative decrease in CD56+CD16+ cells counts and increased apoptosis levels. This function of DCs was partially abrogated in presence of DHEAS. The results obtained reveal new mechanisms of immune/ endocrine nteractions in normal and complicated pregnancy.

Abstract. The aim of this work was to reveal novel criteria for prediction of clinical course in myasthenia, based on immunogenetic characteristics of the patients. Sixty-five patients with different clinical forms, various clinical course and severity of myasthenia were involved into the study. All the patients were subject to complete clinical and neurological examination, and all of them have undergone thymectomy, a histology of thymus has been performed. Immunogenetic studies included HLA class I typing (A and B loci), like as HLA class II typing (DRB* locus). A positive association was found between development of disorder and presence of HLAB8 antigen, HLA-DRB1*03, and their combination, thus allowing for suggesting these specificities as probable markers of genetic predisposition for myasthenia development. An HLA-B7 specificity may have a protective role in evolution of this disease. It was shown that clinical severity in myasthenia and degree of neuromuscular conductive disturbances were more expressed in the patients carrying HLA-B8 antigen and HLA-DRB1*03 allele. Evaluation of immunogenetic state at earlier stages of disorder allows of timely differential diagnostics and individual prediction of clinical variability in myasthenia patients.

Abstract. We have carried out a prevalence analysis of IL6 (-174 G/C) gene promoter polymorphism and traditional cardiovascular risk factors in male patients living in the West Siberia that survived myocardial infarction (MI) in their anamnesis. Analysis of genotype frequencies have shown decrease of *-174 GG genotype in the patients with MI. Frequency of the same genotype is decreased among smoking patients as compared to healthy non-smokers. On other hand, an increased body weight and arterial pressure indexes increase is found in IL6*-174 G patients, versus healthy population. Hence, the analyzed IL6 (-174 G/C) polymorphism may be considered as an additional predisposition factor for development of vascular damage.

Abstract. In present work, an immunocorrective effect of phenotropil after intraperitoneal injection (50 mg/kgx3) was studied in CBA mice. The drug was administered either before antigenic stimulation, and/or cyclophosphamide-induced immunosuppression, or at the terms of evolving immune deficiency. Phenotropil was shown to prevent the development of immune pathology which manifested as inhibition at all steps of immunogenesis, thus suggesting a preventive potential of its immunocorrective properties.

Abstract. A study of cell and humoral immune indices was carried out in forty-five pre-treated patients with multiple myeloma. Imbalance in T:B lymphocyte ratio was revealed, due to increased CD3+ cells and decreased CD20+ cell levels. Accordingly, lowered levels of HLA-DR-lymphocytes, high CD8 cell scores, low percentages of phagocytizing neutrophils, decreased IgM and complement titers, increased serum lysozyme and β-lysine activities were observed. Immune disorders in the patients with II and III stage disease were much more frequent, as compared to stage I, and they depended on immune variant of myeloma. Minimal immune defects were noted in cases with Bence Jones variant. High-dose chemotherapy resulted into more expressed immune disorders, mainly, altered T-cell immunity. These data are indicative for a necessity of a regular immunological monitoring, aiming for administration of immunocorrective therapy.

Abstract. The article contains results of studying the natural inhibitory serum activity in the patients with acute leukemia. A correlation is revealed between a resistance to myelosuppressive therapy, and positive inhibitory reaction towards immunoglobulins M. Determination of IL-2, IL-4 levels, as well as sulfhydril (SH- ) groups and amounts of blast cells at initial stage of disease are of high importance for early diagnosis of drug resistance upon the disease onset.

Abstract. We have studied some features of immune system in children with common episodes of acute respiratory infections accompanied by lymphadenopathies (LAP). Among this cohort of the patients, a decrease in general immune reactions was revealed, accomplished by polyclonal activation of distinct lymphocyte subpopulations. Certain immune changes have been discerned in children with common infections accompanied by a LAP syndrome, such as an increased ratios of T- and B-lymphocytes carrying CD69 and CD25 activation molecules, a CD71 marker typical for proliferating cells, NKT-cells positive for CD3, CD56, CD8 with high cytokine-producing potential, as well as increased rates of spontaneous blast transformation of lymphocytes, both in course of the disease, and following recovery of the children.

Abstract. Seventy-nine children participated in the study including 33 children living in region with developed cement industry (12 with glomerulonephritis, and 21 with obstructive pyelonephritis). A group of comparison consisted of 46 children living in Moscow, including 17 subjects with glomerulonephritis and 29 children with obstructive pyelonephritis, and control group of 26 healthy children. ELISA method was used to perform immunological studies. The levels of sCD4, IL-2, IL-6, IL-10, sICAM-1, TNFα were evaluated in blood sera. The data obtained show significant increase of TNFα levels and decreased IL-6 levels (p < 0,05) in children with nephropathy living in regions with unfavorable environmental conditions as compared with control group. A seven-fold increase in TNFα levels, along with more than twofold decrease in IL-6 was revealed among children with obstructive pyelonephritis, as compared with control group (p < 0,05). In children with glomerulonephritis and obstructive pyelonephritis, a distinct increase of sCD4 , as well as decreased IL-2 level (p < 0,05) was registered, as compared with control group. Meanwhile, IL-10 contents in this group of patients was 22,4 times less than the in controls (p < 0,05). In the main group, no enhanced sICAM synthesis was found, both in children with glomerulonephritis and pyelonephritis. In children affected by adverse environmental pathogens, we have shown a prevailing immune inflammation due to hyperproduction of TNFα, IL-6, and activation of sCD4 helpers. Adverse environmental effects inhibit cytokine synthesis, thus reducing production of both pro- and anti-inflammatory cytokines.