In vivo antiviral effect of interleukin 18 in a mouse model of vaccinia virus infection.
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.
Tanaka-Kataoka
M
M
Fujisaki Institute, Hayashibara Biochemical Laboratories Inc., 675-1 Fujisaki, Okayama, 702-8006, Japan.
Kunikata
T
T
Takayama
S
S
Iwaki
K
K
Ohashi
K
K
Ikeda
M
M
Kurimoto
M
M
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000998:Antiviral Agents / Q000627:therapeutic use*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003602:Cytotoxicity, Immunologic; D005260:Female; D007371:Interferon-gamma / Q000276:immunology / Q000502:physiology*; D020382:Interleukin-18 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000627:therapeutic use; D014615:Vaccinia / Q000276:immunology* / Q000517:prevention & control; D014616:Vaccinia virus / Q000254:growth & development; D014709:Vero Cells; D015431:Weight Loss
D000906:Antibodies; D000998:Antiviral Agents; D020382:Interleukin-18; D011994:Recombinant Proteins; D007371:Interferon-gamma