Immunoregulatory cytokines in chronic hepatitis C virus infection: Pre- and posttreatment with interferon alfa

Abstract

T lymphocytes and immunoregulatory cytokines may be important in the host response to hepatitis C virus (HCV) infection. T-helper type 1 (Th1) cytokines (interleukin [IL]-2, interferon gamma [IFN-gamma]) are required for host antiviral immune responses, including cytotoxic T-cell generation and natural killer cell activation, while T-helper type 2 (Th2) cytokines (IL-4,IL-10) can inhibit the development of these effector mechanisms. In this study, the serum levels of Th1 and Th2 cytokines in patients (n = 23) infected with HCV were measured and compared with biochemical (alanine transaminase [ALT]) and viral (HCV RNA) indicators of infection. Serial cytokine levels were measured in a subset of 11 patients at 1 and 12 weeks during and at 1 week after interferon alfa (IFN-α) therapy (n = 33 samples). Levels of circulating IL-2, IL-4, IL-10, and IFN-γ were significantly elevated in HCV patients versus normal controls (128 vs. 25 pg/mL, 3,045 vs. 29 pg/mL, 2,949 vs. 18 pg/mL, and 307 vs. 24 pg/mL respectively; P < .01). Treatment with IFN-α decreased the levels of IL-4 (321 ± 224 pg/mL), and IL-10 (1,011 ± 344 pg/mL), which paralleled a decrease in HCV RNA (114 ± 27 vs. 25 ± 20 Eq/ml X 105, pre- vs. post-IFN-α [12 weeks];P <.05). These findings indicate that an activated T-cell response, as manifest by increased circulating immunoregulatory cytokines, is present in patients with HCV liver disease. Furthermore, treatment with HCV liver disease. Furthermore, treatment with IFN-α diminishes the Th2 cytokine response. Thus, modulation of T-cell function and cytokine production may be one mechanism whereby IFN-α therapy results in reduced viral burden. (Hepatology 1996 Jul;24(1):6-9)