In vitro effect of thymosin-alpha 1 and interferon-alpha on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C

Current evidence suggests that increased expression of Th1-associated cytok ines is important for immune-mediated eradication of hepatitis C infection, while an increase in Th2-associated cytokines is associated with persisten ce of infection. In this study we evaluated the effects of thymosin-alpha1 (TA1), a naturally occurring thymic peptide, and interferon-alpha (IFN-alph a) on cytokine production in peripheral blood mononuclear cells from untrea ted patients with chronic hepatitis C. We examined the effect of incubation with TA1, IFN-alpha, or both, on production of Th1-associated cytokines (I L-2, IFN-gamma), Th2-associated cytokines (IL-4, IL-10), and synthesis of t he antiviral protein 2',5'-oligoadenylate synthetase. TA1 treatment induced a significant increase in production of IL-2 and 2',5'-oligoadenylate synt hetase. Smaller increases were also seen after treatment with IFN-alpha, wh ile incubation with TA1 and IFN-alpha together led to an additive or synerg istic effect. Incubation with TA1 resulted in a decrease in IL-4 and IL-10, whereas IFN-alpha increased these cytokines. The addition of TA1 to IFN-al pha significantly reversed this IFN-alpha -induced increase. Hence, TA1 tre atment could benefit patients with hepatitis C infection by increasing the Th1-type response, fundamental for sustained clearance of hepatitis C; and by decreasing the Th2-type response, associated with persistence of viraemi a.