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

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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
Volume81
Issue number3
DOIs
StatePublished - Mar 1 2007

Keywords

  • 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. https://doi.org/10.1189/jlb.1006622