In vitro modification of Th1/Th2 balance by interferon-alpha subtypes in peripheral blood mononuclear cells from patients with hepatitis B virus-infection

T helper (Th) cells have been characterized into two subsets, Th1 and Th2, by the pattern of cytokine secretion. Generally, Th1 type cells mediate cellular immune responses and Th2 type cells mediate humoral immunity. Recently, Th1 type immunity is thought to be necessary to exclude hepatitis B virus (HBV). Although enhanced expression of Th1 type cytokine is found in patients after interferon-alpha (IFN-alpha) treatment, the mechanism of this therapeutic effect has not been clarified adequately. In this study we investigated the effects of several IFN-alpha subtypes on the balance between Th1 and Th2 cells in eleven patients with HBV, by stimulating their peripheral blood mononuclear cells (PBMC) with phorbol 12-myristate 13-acetate (PMA) and ionomycin. Cytokine producing cells were determined by flow cytometry after 48 h of stimulation with several IFN-a subtypes. Compared with the control, IFN-alpha2, IFN-alpha8 and IFN-alpha10 exhibited up-regulation of the Th1/Th2 ratio by both increasing the Th1 cell population and/or decreasing the Th2 cell population. IFN-alpha8 was the most potent cytokine for changing the Th1/Th2 balance among the IFN-a subtypes tested. IFN-alpha5, however, revealed an inverse effect and IFN-alpha1 did not show any significant changes. These findings imply that IFN-alpha subtypes modify the Th1/Th2 balance in PBMC from patients with HBV, thus suggesting a useful form of IFN therapy for the HBV-infected patients that have an imbalance between Th1 and Th2 cell populations. Furthermore, our findings should help to elucidate the mechanism underlying IFN therapy for patients with HBV infection.