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Interleukin-18 inhibits hepatitis B virus replication in the livers of transgenic mice

Academic Article
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Overview

authors

  • Kimura, K.
  • Kakimi, K.
  • Wieland, Stefan
  • Guidotti, Luca
  • Chisari, Francis

publication date

  • November 2002

journal

  • Journal of Virology  Journal

abstract

  • Interleukin-18 (IL-18) produced by activated antigen-presenting cells stimulates natural killer (NK) cells, natural killer T (NKT) cells, and T cells to secrete gamma interferon (IFN-gamma). In this study, injection of a single 10- micro g dose of recombinant murine IL-18 rapidly, reversibly, and noncytopathically inhibited hepatitis B virus (HBV) replication in the livers of HBV transgenic mice. Furthermore, HBV replication was inhibited by as little as 1 micro g of IL-18 injected repetitively, and also by a single 0.1- micro g dose of IL-18 injected together with 1 ng of IL-12, neither of which inhibited HBV replication individually, demonstrating synergy between these cytokines in this system. The antiviral effect of IL-18 was mediated by its ability to activate resident intrahepatic NK cells and NKT cells to produce IFN-gamma and by its ability to induce IFN-alpha/beta production in the liver. These results suggest that IL-18 has the potential to contribute to the control of HBV replication during self-limited infection and that it may have therapeutic value for the treatment of patients with chronic hepatitis.

subject areas

  • Animals
  • Antiviral Agents
  • DNA, Viral
  • Drug Synergism
  • Hepatitis B virus
  • Humans
  • Interferon-alpha
  • Interferon-beta
  • Interferon-gamma
  • Interleukin-12
  • Interleukin-18
  • Liver
  • Male
  • Mice
  • Mice, Transgenic
  • Recombinant Proteins
  • Time Factors
  • Virus Replication
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Identity

PubMed Central ID

  • PMC136645

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.76.21.10702-10707.2002

PubMed ID

  • 12368312
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Additional Document Info

start page

  • 10702

end page

  • 10707

volume

  • 76

issue

  • 21

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