Production of interleukins 10 and 12 by peripheral blood mononuclear cells (PBMC) in chronic hepatitis C virus (HCV) infection

We previously reported that interferon-gamma (IFN-γ) production by PBMC in response to HCV core protein was increased in patients with type C chronic liver disease. To understand better the pathophysiology of this disease, we evaluated production of IL-10 and IL-12 by PBMC from 41 patients with chronic HCV infection, including asymptomatic HCV carriers with persistently normal serum ALT values. IL-10 is known to inhibit many effector functions of the immune system, suppressing Th1-type cell development, while IL-12 stimulates differentiation of Th1-type cells, facilitating cell-mediated immunity. IL-10 production was determined by culturing lymphocytes with concanavalin A (Con A), while IL-12 was produced by monocytes in the presence of Staphylococcus aureusCowan 1 (SAC) with or without recombinant HCV core protein, respectively. The cytokine levels in culture supernatants were measured by ELISA. Spontaneous IL-10 production was greater in patients with chronic hepatitis (CH) (229±119 pg/ml, P<0.01) and liver cirrhosis (LC) (185±88 pg/ml, P<0.05) than in controls (119±27 pg/ml), while it was decreased during IFN treatment (70±25 pg/ml). Both HCV core protein and Con A enhanced IL-10 production by cells from HCV-infected patients. IL-12 was not detectable in medium alone cultures, and SAC-induced IL-12 production did not differ between various patient groups and controls. Simultaneous addition of HCV protein resulted in an increase of IL-12 production in chronic liver disease compared with SAC-alone cultures. Addition of IL-10 to the cultures equally suppressed IFN-γ production for both controls and patient groups, but the enhancing effect of IL-12 on IFN-γ production was significantly less in LC than in controls and other patient groups. The findings suggest that secretion of IL-10/IL-12 by cells from control individuals and various patient groups may be different, and that the cytokines might show different effects on IFN-γ production by some cells.