Abstract
The aim of the work was the study of connection of allelic polymorphism of IL10 and TGFВgenes with changes in the basal and BCG-induced production of immunosuppressive cytokines IL-10 and TGF-β by mononuclear leukocytes in vitro in patients with the first diagnosed pulmonary tuberculosis (TB), depending on the clinical form of the disease. The evaluation of the cytokines production was conducted by measuring its concentration in culture supernatants by ELISA. The allele-specific amplification of specific stretches of the genome was used for the study of polymorphic genes of cytokines. The DNA and supernatants of culture suspensions of blood mononuclear leucocytes in healthy volunteers and patients with TB were the material of the research. It was shown in the research conducted that the basal and BCG-induced over-production of IL-10 in vitro occurs in patients with TB, regardless of the genotype of the locus of C-592AIL10 gene. In addition, genotype AA of polymorphism of IL10gene in patients with infiltrative and disseminated TB is associated with the maximum production of IL-10 in vitroand genotype CC – with the minimum production of this cytokine in vitro. Analysis of the production of TGF-β in vitro in patients with TB showed its increase only in case of carriage of allele T (C-509T) of TGFB gene. In patients with disseminated TB and homosygotic genotype TT the increase in both basal and BCG-induced production of TGF-β was determined, and in patients with infiltrative TB – only after induction of cells by BCG-antigen.Thus, the over-production of cytokines with inhibiting activity in patients with TB is genetically determined and promotes the formation of suppressive mode of immune-regulation. The increase in the secretion of cytokines IL-10 and TGF-β in vitro in patients with TB are associated with carriage of allele A and genotype AA (C-592A) of IL10gene and allele T and genotype TT (C-509T) of TGFB gene.
Highlights
The aim of the work was the study of connection of allelic polymorphism of IL10 and TGFBgenes with changes in the basal and BCG-induced production of immunosuppressive cytokines IL-10 and TGF-p by mononuclear leukocytes in vitro in patients with the first diagnosed pulmonary tuberculosis (TB), de pending on the clinical form of the disease
The evaluation of the cytokines production was conducted by measuring its concentration in culture supernatants by ELISA
The allele-specific amplification of specific stretches of the genome was used for the study of polymorphic genes of cytokines
Summary
ПОЛИМОРФИЗМ ГЕНОВ ИММУНОСУПРЕССОРНЫХ ЦИТОКИНОВ IL-10 И TGF-P ПРИ ТУБЕРКУЛЕЗНОЙ ИНФЕКЦИИ. Целью работы явилось исследование связи аллельного полиморфизма генов IL10 и TGFBc измене ниями базальной и BCG-индуцированной продукции соответствующих иммуносупрессорных цитокинов IL-10 и TGF-p мононуклеарными лейкоцитами in vitro у пациентов с впервые выявленным туберкулезом легких (ТБ) в зависимости от клинической формы заболевания. Анализ продукции TGF-p in vitro у больных ТБ показал ее увеличение только в случае носительства аллеля Т(С -509Т) гена TGFB. При этом выраженное увеличение секреции цитокинов IL-10 и TGF-p in vitro у больных ТБ ассоциировано с носительством аллеля А и генотипа А А (С-592А) гена IL10 и аллеля Т и ге нотипа Т Т (С-509Т) гена TGFB. Поскольку экзонные последовательности генов цитокинов очень консервативны, а экспрессия соот ветствующего участка генома непосредственно кон тролируется его промотором, целью работы явилось исследование у больных ТБполиморфизмов промоторных регионов генов IL10 и TGFB, которые влияютна количество генного продукта (продукцию клетками иммуносупрессорных цитокинов IL-10 и T G F-p),но не изменяют аминокислотной последовательности белка и его функций
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