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DOI: 10.1055/s-0032-1312416
IL28B CC genotype is associated with increased TH1 but not TH2 type cytokine production by peripheral blood mononuclear cells in chronic HCV1 infection
Background: IL28B CC genotype is the strongest pretreatment predictor of SVR in HCV1 patients treated with PEG-IFN and ribavirin. IL28B CC also associated with improved early viral kinetics and greater likelihood of rapid virological response (RVR) compared with CT or TT genotypes. Since the immunological mechanisms underlying the observed relationship between IL28B genotype, RVR and SVR remain unknown the aim of the present study was to compare peripheral blood monocytes and lymphocytes IFN-gamma, TNF-alfa, IL-2, IL-4, IL-6, IL-10 cytokine production of patients with IL28B CC, CT and TT haplotypes.
Methods: Fourty HCV-1 patients were genotyped as CC (n=12), CT (n=20) or TT (n=8) at polymorphic site of IL28B rs12979860. IFN-gamma, TNF-alfa, IL-2, IL-4, IL-6, IL-10 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. In patients with CC genotype we found increased Th1 type cytokine production of peripheral blood lymphocytes compared to non CC genotype groups. Lymphocyte TNF-alfa, IL-2, IFNgamma production were significantly higher in CC patients compared to CT and TT groups (CC: TNF-alfa: 14.6ng/ml, IL2: 156.9ng/ml, IFNgamma: 225.7ng/ml, CT: TNF-alfa: 7.1ng/ml, IL2: 40.5ng/ml, IFNgamma: 94.8ng/ml, TT: TNF-alfa: 6.9ng/ml, IL2: 37.9ng/ml, IFNgamma: 109.2ng/ml p<0.01). Peripheral blood monocytes and lymphocytes IL-4, IL-6, IL-10 production 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, IL-2 and IFN-gamma 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 antiviral cytokine production of both lymphocytes and monocytes. We suppose that in IL28CC variants the increased inducible antiviral cytokine production may play a crucial role in rapid immune control of HCV infection and favour sustained virological response.