HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print December 15, 2006

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.1006622v1 81/3/825    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Byrnes, A. A. Articles by Karp, C. L. Search for Related Content PubMed PubMed Citation Articles by Byrnes, A. A. Articles by Karp, C. L.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1006622

Received for publication October 9, 2006.
Revised November 1, 2006.
Accepted for publication November 8, 2006.

Article

Modulation of the IL-12/IFN- axis by IFN- 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 , and Christopher L. Karp ^***@

Departments of *Medicine and Molecular Microbiology and Immunology and Pediatrics, Johns Hopkins University, Baltimore, Maryland, USA; Maryland Medical Research Institute, Baltimore, Maryland, USA; Departments of Pediatrics and Pathology and Laboratory Medicine, Children’s National Medical Center, George Washington University School of Medicine, Washington, DC, USA; ^||Division of Gastroenterology, Riley Hospital for Children, Indiana University Medical Center, Indianapolis, Indiana, USA; ^¶Department of Pediatrics, University of Colorado Health Sciences Center, and The Pediatric Liver Center, The Children’s Hospital, Denver, Colorado, USA; ^#Wyeth Research, Cambridge, Massachusetts, USA; and **Division of Molecular Immunology, Cincinnati Children’s Hospital Research Foundation, and the University of Cincinnati, Cincinnati, Ohio, USA

^@ To whom correspondence should be addressed. E-mail: chris.karp{at}chmcc.org.

	Abstract

Although IFN- forms the foundation of therapy for chronic hepatitis C, only a minority of patients has a sustained response to IFN- alone. The antiviral activities of IFN- formed the rationale for its use in viral hepatitis. However, IFN- and the other Type I IFNs are also pleiotropic immune regulators. Type I IFNs can promote IFN- production by activating STAT4 but can also inhibit production of IL-12, a potent activator of STAT4 and IFN- production. The efficacy of IFN- in the treatment of hepatitis C may therefore depend in part on the balance of IFN--inducing and IL-12-suppressing effects. We characterized the effects of pegylated IFN- therapy for hepatitis C on the capacity of patients’ PBMC to produce IL-12 and IFN- ex vivo. Cells from patients with a sustained virological response to therapy had significantly greater levels of IFN--driven IFN- 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- led to suppression of inducible IL-12 production throughout the course of therapy in both groups of patients.

Key Words: immunomodulation • cytokine • memory T cell • IFN-