Association between polymorphisms of cytokine genes and secretion of IL-12p70, IL-18, and IL-27 by dendritic cells in patients with pulmonary tuberculosis.

Proinflammatory cytokines are known to play a crucial role in the pathogenesis of tuberculosis, and gene polymorphisms in the promoter regions of cytokine genes were shown to substantially influence the secretory capacity of immune cells. In the present study, we analyzed the association between polymorphisms of the IL12B, IL18, and IL27 genes and the secretion of the proinflammatory cytokines IL-12р70, IL-18, and IL-27 by myeloid dendritic cells (mDCs) in pulmonary tuberculosis (PTB) patients. The study enrolled 334 patients with newly diagnosed infiltrative and disseminated PTB. Cultivation of mDCs was performed from non-proliferating progenitors of CD14+ blood monocytes. Cytokine secretion was evaluated by measuring cytokine concentration in the mDC culture supernatants using enzyme-linked immunosorbent essay (ELISA). To study cytokine gene polymorphisms, a polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP) were performed. Reduced secretion of IL-18 and IL-27 by mDCs in PTB patients was associated with 105A/C polymorphisms of the IL18 gene, and 2905T/G, 4730T/С, and -964A/G of the IL27 gene, respectively. Polymorphism IL12B/insertion had a bidirectional influence on the secretion of IL-12p70, being associated with decreased levels of the cytokine in infiltrative PTB and increased levels in disseminated PTB patients.

The role of foxp3-expressing regulatory T cells and T helpers in immunopathogenesis of multidrug resistant pulmonary tuberculosis.

Subpopulation structure of regulatory T cells and T helpers of peripheral blood in patients with newly diagnosed pulmonary tuberculosis depending on the clinical form of disease and sensitivity of Mycobacterium tuberculosis to antituberculosis drugs has been analyzed in this work. It has been shown that the leading part in immune suppression at infiltrative, dissemination, and fibrosis-cavity pulmonary tuberculosis is played by natural regulatory CD4(+)CD25(+)Foxp3(+)-T lymphocytes. Thus we estimate increase of their number in blood by drug-resistance and drug-susceptible patients. It has been demonstrated that in patients with fibrocavernous and infiltrative form of the disease and drug-resistant pulmonary tuberculosis the number of CD4(+)CD25(-)Foxp3(+)-regulatory T cells was increasing. In patients with infiltrative pulmonary tuberculosis, including multidrug-resistant M. tuberculosis, an increased number of CD3(+)CD4(+)CD25(-) T helpers is determined by the pathogenic features of the development of the tuberculosis infection and is connected with the activation of Th1-dependent immune response. Reduction in the number of T-helpers in the blood of patients with dissemination and fibrosis-cavity pulmonary tuberculosis mediates inefficient implementation of cell-mediated protective immunity.

Effect of chelating agents and stress factors on zinc content in paneth cells and prostate gland cells.

The effects of chelating agents dithizone and sodium diethyldithiocarbamate on zinc content in Paneth cells and prostate gland cells were studied on rats preliminary exposed to stress factors (exercise and immobilization). Dithizone induced irreversible triphasic and sodium diethyldithiocarbamate reversible biphasic changes in zinc metabolism in cells. Preliminary stress potentiated the damaging effect of dithizone.

Assessment of the relationship of chronic opisthorchiasis to Epstein-Barr virus infection as well as some cytogenetical and immunological parameters in two comparable Siberian regions.

Previous studies have shown an increase in the frequency of chromosomal abnormalities in the peripheral blood lymphocytes from opisthorchiasis patients. Some evidence suggests that there is an association between chronic opisthorchiasis and certain herpes viruses. To study the relationship of opisthorchiasis to the reactivation of Epstein-Barr virus (EBV) infection as well as the influence of opisthorchis infection on some cytogenetical and immunological parameters, we used the indirect immunofluorescence for measuring some virus specific antibodies, the cytokinesis-block lymphocyte micronucleus assay, and the quantitative immunodiffusion method for measuring immunoglobulin concentrations in serum. A total of 1,580 people were monitored in two comparable Siberian regions: in the Ob River region which is endemically related to opisthorchiasis caused by Opisthorchisfelineus and in the nonendemic control Yenisey River region. There was no significant difference in each of the tested parameters between two uninfected controls from the endemic Ob and nonendemic Yenisey regions. We have found significant difference (p < 0.01) in the frequency of micronucleated cytokinesis-block lymphocytes and the antibody levels against certain EBV antigens between the examined inhabitants of the opisthorchis-infected Ob and uninfected Yenisey regions. Furthermore, there were a good correlation (r = + 0.72) between the increase in titres of antibody to the EBV capsid antigen and the high frequency of micronucleated lymphocytes in the opisthorchis-infected Ob population. Also, levels of both IgG and IgM were increased in opisthorchiasis patients. This study confirms an association between chronic opisthrochiasis and reactivation of EBV which may be implicated in the development of cancer in opisthorchiasis patients.