Interleukin-18 improves the early defence system against influenza virus infection by augmenting natural killer cell-mediated cytotoxicity Liu, Beixing and Mori, Isamu and Hossain, Md Jaber and Dong, Li and Takeda, Kiyoshi and Kimura, Yoshinobu,, 85, 423-428 (2004), doi = https://doi.org/10.1099/vir.0.19596-0, publicationName = Microbiology Society, issn = 0022-1317, 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-γ) 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., language=, type=