In vitro effects of interferon-alpha subtypes on the Th1/Th2 balance in the peripheral blood mononuclear cells from patients with hepatitis C virus infection

Enhanced T helper I (Th1)-type immunity was observed in patients with hepatitis C virus (HCV) infection during investigations on the efficiency of interferon (IFN) therapy. The mechanism for the shift to Th1-type immunity is, however, obscure in HCV infection. In this study, we examined the in vitro effect of IFN-alpha subtypes (IFN-alpha 1, -alpha 2, -alpha 5, -alpha 8 and -alpha 10) on the Th1/Th2 balance in the peripheral blood mononuclear cells (PBMC) obtained from healthy control volunteers and HCV-infected patients. A two-day incubation without IFN stimulation did raise the Th1-type cell percentage but not the Th2-type cell percentage in the PBMC of the control group. The Th1-type cell percentage and Th1/Th2 ratio were significantly larger in the PBMC of patients when compared to controls both before and after treatment with the IFNs. IFN-alpha 5 treatment induced an increase of the Th2-type cell percentage in both control and patient PBMC but did not show any significant changes in the Th1/Th2 ratio. Furthermore, IFN-alpha 8 treatment slightly promoted an increase in the Th1/Th2 ratio only in patient PBMC. Statistical analysis revealed that effects of the IFN-a subtypes on the Th1/Th2 balance differed between two patient groups with severe liver damage (alanine aminotransferase; ALT: >= 80 IU/ml) and mild liver damage (ALT: < 80 IU/ml). IFN-alpha 5 treatment lowered the Th1/Th2 ratio in patients with mild liver damage, whereas IFN-alpha 8 treatment raised the Th1/Th2 ratio in patients with severe liver damage without IFN-alpha 5-induced decrease in the ratio. These findings imply that HCV infection and its disease status modify the effects of IFN-alpha subtypes on Th1 and Th2 immune balance in patients. Our findings should help to elucidate the mechanisms underlying IFN therapy for HCV infection.