In vivo antiviral effect of interleukin 18 in a mouse model of vaccinia virus infection

Cytokine. 1999 Aug;11(8):593-9. doi: 10.1006/cyto.1998.0453.


Interleukin-18 (IL-18), originally called interferon-gamma (IFN-gamma)-inducing factor is a novel cytokine which exhibits pleiotropic immunomodulatory activities such as the activation of natural killer (NK) cells and cytotoxic T lymphocytes (CTL). In this study, the efficacy of IL-18 on viral infection in mice was investigated. IL-18 treatment significantly suppressed pock formation on the tails of BALB/c mice inoculated intravenously with vaccinia virus when the cytokine was administered intraperitoneally on days 0, 2 and 4 after infection. Sequentially, NK and CTL activity of the infected mice were significantly augmented by IL-18 injection. The in vivo anti-vaccinia virus activity of IL-18 was only partially inhibited by treating the infected mice with anti-asialo GM1 antibody. When infected mice were injected with anti-IFN-gamma antibody only, severe deterioration of health and significant body weight loss were observed, suggesting that IFN-gamma is very important in protecting mice against vaccinia virus infection. Interestingly, IL-18 injection visibly improved the severe vaccinia virus-induced symptoms in mice treated with anti-IFN-gamma antibody, even though a pivotal involvement of IFN-gamma in IL-18-mediated anti-vaccinia virus effect is not yet determined. Taken together, these results indicate that the IL-18-elicited anti-vaccinia virus effect in the acute phase of infection would be raised by the sum of various host defence mechanisms including NK cells and CTL, and not from a specific immunocompetent cell population or effector molecule.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Antiviral Agents / therapeutic use*
  • Cell Line
  • Chlorocebus aethiops
  • Cytotoxicity, Immunologic
  • Female
  • Interferon-gamma / immunology
  • Interferon-gamma / physiology*
  • Interleukin-18 / therapeutic use*
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Proteins / therapeutic use
  • Vaccinia / immunology*
  • Vaccinia / prevention & control
  • Vaccinia virus / growth & development
  • Vero Cells
  • Weight Loss


  • Antibodies
  • Antiviral Agents
  • Interleukin-18
  • Recombinant Proteins
  • Interferon-gamma