Interleukin 12 enhances deficient HCV-antigen-induced Th1-type immune response of peripheral blood mononuclear cells

The aim of this study was to examine the possible immunomodulating effects of rhIL-12 on the immune response induced by different hepatitis C virus (HCV) antigens. Freshly isolated peripheral blood mononuclear cells (PBMC) of 33 patients with chronic HCV infection were stimulated with optimal concentrations of antigens from the NS3, NS4, NS5, and core region of HCV in the absence or presence of interleukin-12 (IL-12). Stimulation by alpha-CD3 + alpha-CD28, lipopolysaccharide (LPS), and pokeweed mitogen (PWM) were used as controls. Proliferation and cytokine production were determined by 3H-thymidine uptake and enzyme-linked immunosorbent assay (ELISA) after 72 hr. After stimulation with antigen or antigen + IL-12, increased proliferation and production of interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha) were observed in 23 of the 33 patients. Thus, a separation of the patients into HCV-antigen/IL-12 responders (group 1, n = 23) and HCV-antigen/IL-12 nonresponders (group 2, n = 10) was possible. Lower baseline IL-12- and LPS-induced IFN gamma, TNF alpha, and IL-12 production was observed in group 2 due to a possible dysfunction of accessory cells. Significant antigen-induced Th2-type cytokine (IL-4, IL-10, IL-13) production was not found. According to clinical and serological parameters, group 2 comprised mostly patients with advanced liver disease. These data suggest an HCV-related cellular immune defect in patients with hepatitis C that can be restored in most patients by IL-12.