Effect of IL-12 on T-cell immune responses in patients with chronic HCV infection

As the host's immune responses may determine the outcome of hepatitis C vir us (HCV) infection, and interleukin (IL)-12 plays an essential role in host defense against infectious diseases, we studied the antigen-specific and n on-specific cellular immune responses in patients with chronic HCV infectio n. A proliferative response to phytohemagglutinin (PHA) was found in all 20 patients. Of the 20, 8 (40%) displayed a lymphocyte proliferation in respo nse to HCV antigen c22, 2 (10%) to c33, 6 (30%) to c100-3, and 1 (5%) to NS 5. The addition of rhIL-12 to cultures of peripheral blood mononuclear cell s (PBMC) stimulated with PHA significantly enhanced the proliferative respo nses in normal controls as well as in HCV-infected subjects. The increased proliferation was also observed in HCV-infected patients when PBMC were co- cultured with HCV antigens c22 and c100-3 in the presence of rhIL-12. The p roduction of interferon gamma (IFN gamma), IL-2, IL-4 and IL-10 was observe d in 7 (58.3%), 5 (41.7%), 3 (25.0%) and 5 (41.7%) HCV-infected individuals stimulated with c22, and in 4 (33.3%), 2 (16.7%), 2 (16.7%) and 2 (16.7%) with c100-3, respectively. All HCV-infected individuals had increased produ ction of cytokines IFN gamma, IL-2, IL-4 and IL-10 in supernatants of PBMC after stimulation with PHA. IL-12 significantly augmented Th1 cytokine prod uction in HCV-infected individuals stimulated with PHA and with HCV antigen s. In conclusion, deficient cellular immune responses are present in HCV-in fected patients and IL-12 can enhance the immune responses in these patient s.