Modulation of the IL-12/IFN-γ axis by IFN-α therapy for hepatitis C

Adriana A. Byrnes, Ding You Li, Kiwon Park, Douglas Thompson, Cathleen Mocilnikar, Parvathi Mohan, Jean P. Molleston, Michael Narkewicz, Huanfang Zhou, Stanley F. Wolf, Kathleen B. Schwarz, Christopher L. Karp

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13 Scopus citations


Although IFN-α forms the foundation of therapy for chronic hepatitis C, only a minority of patients has a sustained response to IFN-α alone. The antiviral activities of IFN-α formed the rationale for its use in viral hepatitis. However, IFN-α and the other Type I IFNs are also pleiotropic immune regulators. Type I IFNs can promote IFN-γ production by activating STAT4 but can also inhibit production of IL-12, a potent activator of STAT4 and IFN-γ production. The efficacy of IFN-α in the treatment of hepatitis C may therefore depend in part on the balance of IFN-γ-inducing and IL-12-suppressing effects. We characterized the effects of pegylated IFN-α therapy for hepatitis C on the capacity of patients' PBMC to produce IL-12 and IFN-γ ex vivo. Cells from patients with a sustained virological response to therapy had significantly greater levels of IFN-α-driven IFN-γ production prior to treatment than those from nonresponding patients. No differences in pretreatment IL-12 productive capacity were seen between patient groups. However, therapy with IFN-α led to suppression of inducible IL-12 production throughout the course of therapy in both groups of patients.

Original languageEnglish (US)
Pages (from-to)825-834
Number of pages10
JournalJournal of Leukocyte Biology
Issue number3
StatePublished - Mar 1 2007


  • Cytokine
  • IFN-β
  • Immunomodulation
  • Memory T cell

ASJC Scopus subject areas

  • Cell Biology

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    Byrnes, A. A., Li, D. Y., Park, K., Thompson, D., Mocilnikar, C., Mohan, P., Molleston, J. P., Narkewicz, M., Zhou, H., Wolf, S. F., Schwarz, K. B., & Karp, C. L. (2007). Modulation of the IL-12/IFN-γ axis by IFN-α therapy for hepatitis C. Journal of Leukocyte Biology, 81(3), 825-834.