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Modulation of the IL‐12/IFN‐γ axis by IFN‐α therapy for hepatitis C
Author(s) -
Byrnes Adriana A.,
Li DingYou,
Park Kiwon,
Thompson Douglas,
Mocilnikar Cathleen,
Mohan Parvathi,
Molleston Jean P.,
Narkewicz Michael,
Zhou Huanfang,
Wolf Stanley F.,
Schwarz Kathleen B.,
Karp Christopher L.
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1006622
Subject(s) - alpha interferon , immunology , biology , immune system , alpha (finance) , interferon alfa , cytokine , interferon gamma , peripheral blood mononuclear cell , hepatitis b , hepatitis c , hepatitis , interferon , medicine , in vitro , construct validity , biochemistry , nursing , patient satisfaction
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.