Immunopathogenesis of chronic viral hepatitides was studied by modern immunological, molecular, genetic methods. We revealed an imbalance in the production of immunoregulatory cytokines by mononuclear leukocytes (primarily of the Th2 type). The risk of progression and chronic course of viral hepatitides in Caucasian population was associated with alleles of promoter regions -330G and -592A in the IL-2 and IL-10 genes, respectively, as well as with the T/T genotype of the polymorphic region C590T in the IL-4 gene. The C/C genotype of the IL-10 gene promoter region C592A was shown to be a factor determining resistance to long-term persistence of hepatitis B and C viruses.
The effect of recombinant TNF-α on programmed death of donor lymphocytes was studied in vitro. The proapoptotic effect of this cytokine is realized through transcription factors and cell cycle inhibitors. Incubation of lymphocytes with recombinant TNF-α revealed increased levels of NF-kB and p21 and reducted content of nonphosphorylated p53.
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