title: Interleukin-18 improves the early defence system against influenza virus infection by augmenting natural killer cell-mediated cytotoxicity.
abstract: 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.
authors.affiliation: Department of Microbiology, Fukui Medical University School of Medicine, Shimoaisuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
authors.forename: Beixing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Fukui Medical University School of Medicine, Shimoaisuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Mori
authors.affiliation: Department of Microbiology, Fukui Medical University School of Medicine, Shimoaisuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
authors.forename: Md Jaber
authors.initials: MJ
authors.lastname: Hossain
authors.affiliation: Department of Microbiology, Fukui Medical University School of Medicine, Shimoaisuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
authors.forename: Li
authors.initials: L
authors.lastname: Dong
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Microbiology, Fukui Medical University School of Medicine, Shimoaisuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kimura
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D009980:Influenza A virus; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D020382:Interleukin-18 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D011014:Pneumonia / Q000276:immunology; D012137:Respiratory System / Q000276:immunology
chemical_list: D020382:Interleukin-18; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma