Interleukin-12 p40/p70 Ratio and In Vivo Responsiveness to IFN- α Treatment in Chronic Hepatitis C

Abstract

To evaluate the relationship between cytokine balance and responsiveness to interferon-α (IFN-α), we investigated the production of IFN-γ, interleukin-10 (IL-10), IL-12 p70, and IL-12 p40 by peripheral blood mononuclear cell (PBMC) cultures from patients with chronic hepatitis C (CHC) before and after 1 year of IFN-α treatment. Before the therapy, responder(R) patients exhibited lower IFN-γ release, higher IL-10 production, and higher values of the IL12 p40/p70 ratio compared with nonresponders (NR). Increased sensitivity to the effects of IL-12 and IL-10, as well as higher IL-12-dependent IFN-γ secretion, were also found in the R subset. After IFN-α therapy, an increase in IFN-γ production and a decrease in the IL-12 p40/p70 ratio were observed in R patients, whereas opposite results were obtained in the NR group. Finally, the therapy induced downregulation of IL-10 production and cell responsiveness to recombinant IL-12 in all patients. These findings imply that predominance of a T helper 2 (Th2) cytokine profile in CHC patients favors the beneficial effects of IFN-α, thus suggesting a therapeutic role for Th1-driven stimulation of immune response. The findings also stress the primary importance of the IL-12 p40 and p70 balance in the modulation of immune responses to hepatitis C virus (HCV).