Immunoregulatory Cytokines in Chronic Hepatitis C Virus Infection: Pre- And Posttreatment With Interferon Alfa

Hepatology. 1996 Jul;24(1):6-9. doi: 10.1002/hep.510240102.

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-alpha) therapy (n = 33 samples). Levels of circulating IL-2, IL-4, IL-10, and IFN-gamma 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-alpha 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 10(5), pre- vs. post-IFN-alpha [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-alpha diminishes the Th2 cytokine response. Thus, modulation of T-cell function and cytokine production may be one mechanism whereby IFN-alpha therapy results in reduced viral burden.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Alanine Transaminase / blood
  • Cytokines / blood*
  • Follow-Up Studies
  • Hepacivirus / isolation & purification*
  • Hepatitis C / blood
  • Hepatitis C / immunology*
  • Hepatitis C / therapy*
  • Humans
  • Interferon-alpha / therapeutic use*
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / blood
  • Interleukin-2 / blood
  • Interleukin-4 / blood
  • RNA, Viral / blood
  • Reference Values
  • Time Factors

Substances

  • Cytokines
  • Interferon-alpha
  • Interleukin-2
  • RNA, Viral
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma
  • Alanine Transaminase