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 Molleston, Michael Narkewicz, Huanfang Zhou, Stanley F. Wolf, Kathleen B. Schwarz, Christopher L. Karp

Research output: Contribution to journalArticle

13 Citations (Scopus)

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
Pages (from-to)825-834
Number of pages10
JournalJournal of Leukocyte Biology
Volume81
Issue number3
DOIs
StatePublished - Mar 1 2007

Fingerprint

Interleukin-12
Hepatitis C
Therapeutics
Chronic Hepatitis C
Hepatitis
Antiviral Agents

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Byrnes, A. A., Li, D. Y., Park, K., Thompson, D., Mocilnikar, C., Mohan, P., ... 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

Modulation of the IL-12/IFN-γ axis by IFN-α therapy for hepatitis C. / Byrnes, Adriana A.; Li, Ding You; Park, Kiwon; Thompson, Douglas; Mocilnikar, Cathleen; Mohan, Parvathi; Molleston, Jean; Narkewicz, Michael; Zhou, Huanfang; Wolf, Stanley F.; Schwarz, Kathleen B.; Karp, Christopher L.

In: Journal of Leukocyte Biology, Vol. 81, No. 3, 01.03.2007, p. 825-834.

Research output: Contribution to journalArticle

Byrnes, AA, Li, DY, Park, K, Thompson, D, Mocilnikar, C, Mohan, P, Molleston, J, Narkewicz, M, Zhou, H, Wolf, SF, Schwarz, KB & Karp, CL 2007, 'Modulation of the IL-12/IFN-γ axis by IFN-α therapy for hepatitis C', Journal of Leukocyte Biology, vol. 81, no. 3, pp. 825-834. https://doi.org/10.1189/jlb.1006622
Byrnes AA, Li DY, Park K, Thompson D, Mocilnikar C, Mohan P et al. Modulation of the IL-12/IFN-γ axis by IFN-α therapy for hepatitis C. Journal of Leukocyte Biology. 2007 Mar 1;81(3):825-834. https://doi.org/10.1189/jlb.1006622
Byrnes, Adriana A. ; Li, Ding You ; Park, Kiwon ; Thompson, Douglas ; Mocilnikar, Cathleen ; Mohan, Parvathi ; Molleston, Jean ; Narkewicz, Michael ; Zhou, Huanfang ; Wolf, Stanley F. ; Schwarz, Kathleen B. ; Karp, Christopher L. / Modulation of the IL-12/IFN-γ axis by IFN-α therapy for hepatitis C. In: Journal of Leukocyte Biology. 2007 ; Vol. 81, No. 3. pp. 825-834.
@article{9d9e71d47bf942658c9d3d93bf6d75cb,
title = "Modulation of the IL-12/IFN-γ axis by IFN-α therapy for hepatitis C",
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.",
keywords = "Cytokine, IFN-β, Immunomodulation, Memory T cell",
author = "Byrnes, {Adriana A.} and Li, {Ding You} and Kiwon Park and Douglas Thompson and Cathleen Mocilnikar and Parvathi Mohan and Jean Molleston and Michael Narkewicz and Huanfang Zhou and Wolf, {Stanley F.} and Schwarz, {Kathleen B.} and Karp, {Christopher L.}",
year = "2007",
month = "3",
day = "1",
doi = "10.1189/jlb.1006622",
language = "English",
volume = "81",
pages = "825--834",
journal = "Journal of Leukocyte Biology",
issn = "0741-5400",
publisher = "FASEB",
number = "3",

}

TY - JOUR

T1 - Modulation of the IL-12/IFN-γ axis by IFN-α therapy for hepatitis C

AU - Byrnes, Adriana A.

AU - Li, Ding You

AU - Park, Kiwon

AU - Thompson, Douglas

AU - Mocilnikar, Cathleen

AU - Mohan, Parvathi

AU - Molleston, Jean

AU - Narkewicz, Michael

AU - Zhou, Huanfang

AU - Wolf, Stanley F.

AU - Schwarz, Kathleen B.

AU - Karp, Christopher L.

PY - 2007/3/1

Y1 - 2007/3/1

N2 - 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.

AB - 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.

KW - Cytokine

KW - IFN-β

KW - Immunomodulation

KW - Memory T cell

UR - http://www.scopus.com/inward/record.url?scp=33847775588&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847775588&partnerID=8YFLogxK

U2 - 10.1189/jlb.1006622

DO - 10.1189/jlb.1006622

M3 - Article

VL - 81

SP - 825

EP - 834

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

SN - 0741-5400

IS - 3

ER -