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DOI: 10.1055/s-0031-1278496
Association between IL28B CC genotype and increased TNF-alfa and IL-2 production of peripheral blood mononuclear cells in patients with chronic hepatitis C virus (HCV) infection
Background/Aims: Recently IL28B rs12979860 CC genotype as the strongest pretreatment predictor of SVR has been described in HCV genotype 1 patients treated with pegylated interferon and ribavirin. IL28B CC genotype is known to be associated with improved early viral kinetics and greater likelihood of rapid virological response (RVR) compared with CT or TT genotypes. Earlier we demostrated pretreatment TLR4 activation induced TNF-alfa production of the monocytes is significantly higher in RVR patients compared to non-responders. Aim of the present study was to compare cytokine production of patients with IL28B CC, CT and TT genotypes.
Methods: Thirty HCV-1 patients were genotyped as CC (n=8), CT (n=14) or TT (n=8) at polymorphic site of IL28B rs12979860. IFN-gamma, TNF-alfa, IL-2, IL-4, IL-6, production of LPS stimulated peripheral blood monocytes and PMA+ionomycine stimulated lymphocytes were determined by FACS-CBA assay in each genotype group.
Results: LPS induced TLR4 activation of the monocytes resulted in significantly higher TNF-alfa production in patients with CC genotype compared to CT and TT variants (1.53 vs. 0.66 and 0.61ng/ml). In patients with CC genotype, increased Th1 type cytokine production of lymphocytes was also found compared to non CC genotype groups. IL-2 and TNF-alfa production were significantly higher in CC patients compared to CT and TT groups (CC: IL-2: 102ng/ml, TNF-alfa: 21.7ng/ml, CT: IL-2: 42.7, TNF-alfa: 9ng/ml, and TT: IL-2: 37.3ng/ml, TNF-alfa 7ng/ml, p<0.05). IL-6 and IL-4 levels did not differ between study groups.
Conclusion: HCV1 infected patients with IL28B CC genotype had significantly increased LPS induced TNF-alfa production by monocytes, and increased TNF-alfa and IL-2 production of the lymphocytes compared to patients with CT or TT variants. Our data suggest that IL28B CC genotype is associated with increased Th1 type cytokine production that may play a role in the rapid immune control of HCV infection.