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

• Published in: Journal of general virology 2004-02, Vol.85 (2), p.423-428
• Main Authors: Liu, Beixing, Mori, Isamu, Hossain, Md Jaber, Dong, Li, Takeda, Kiyoshi, Kimura, Yoshinobu
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bronchoalveolar Lavage Fluid - immunology; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; 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; Microbiology; Miscellaneous; Nitric Oxide - metabolism; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - mortality; Orthomyxoviridae Infections - pathology; Pneumonia - immunology; Respiratory System - immunology; Virology
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.19596-0

1 Department of Microbiology, Fukui Medical University School of Medicine, Shimoaisuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan 2 Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan Correspondence Yoshinobu Kimura ykimura{at}fmsrsa.fukui-med.ac.jp 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- ) 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.