ПОЛИМОРФИЗМ ГЕНОВ ИММУНОСУПРЕССОРНЫХ ЦИТОКИНОВ IL-10 И TGF-β ПРИ ТУБЕРКУЛЕЗНОЙ ИНФЕКЦИИ

Abstract

The aim of the work was the study of connection of allelic polymorphism of  IL10  and  TGF В genes 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  IL10 gene in patients with infiltrative and disseminated TB is associated with the maximum production of IL-10  in vitro and 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  IL10 gene and allele  T  and genotype  TT  ( C-509T ) of  TGFB  gene.