Interleukin-18 improves the early defence system against influenza virus infection by augmenting natural killer cell-mediated cytotoxicity

J Gen Virol. 2004 Feb;85(Pt 2):423-428. doi: 10.1099/vir.0.19596-0.


The role of interleukin (IL)-18 in the development of the host defence system against influenza virus infection was investigated. IL-18-deficient (IL-18(-/-)) C57BL/6 mice that were inoculated intranasally with the mouse-adapted strain of human influenza A/PR/8/34 (H1N1) virus showed an increased mortality with the occurrence of pathogenic changes in the lung for the first 3 days of infection, which included pronounced virus growth with massive infiltration of inflammatory cells and elevated nitric oxide production. The interferon-gamma (IFN-gamma) level induced in the respiratory tract of IL-18(-/-) mice in the first few days after virus infection was significantly lower but, in contrast, the IL-12 level was slightly higher than the corresponding levels in wild-type C57BL/6 mice. Natural killer (NK) cell-mediated cytotoxicity in the lung of IL-18(-/-) mice was poorly activated. Local immune responses in the lung such as specific cytotoxic T lymphocyte and antibody production were induced upon influenza virus infection equally well in both strains of mice. These results indicate that IL-18 is involved in controlling influenza virus replication in the lung, especially at an early stage of infection, through activation of the innate immune mechanisms such as IFN and NK cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Disease Models, Animal
  • Influenza A virus*
  • Interferon-gamma / analysis
  • Interleukin-12 / analysis
  • Interleukin-18 / deficiency
  • Interleukin-18 / genetics
  • Interleukin-18 / immunology*
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide / metabolism
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / mortality
  • Orthomyxoviridae Infections / pathology
  • Pneumonia / immunology
  • Respiratory System / immunology


  • Interleukin-18
  • Interleukin-12
  • Nitric Oxide
  • Interferon-gamma