title: The protective effects of intranasal administration of IL-12 given before influenza virus infection and the negative effects of IL-12 treatment given after viral infection.
abstract: To investigate whether the administration of IL-12 is effective against influenza virus infection, mice were intranasally administered IL-12 for three consecutive days and then infected with a non-lethal dose of the influenza virus. The IL-12-treated mice were more resistant to the virus than control mice with respect to the remission of body weight loss, virus burden, pro-inflammatory cytokine production, and inflammatory cell infiltration in the lungs. The number of NK cells and the level of NK cell cytotoxicity significantly increased in the lungs of the mice treated with IL-12 before infection compared to that observed in control mice, leading to promptly eliminate the viral-infected cells. Unexpectedly, all of mice that received IL-12 treatment after being infected with a non-lethal dose of the virus died as a result of their high virus burden and pro-inflammatory cytokine production in the lungs. One possibility of the mechanisms was considered to be activation of myeloid-derived suppressor cell (MDSC), which has immune suppressive function, in the lungs. Thus, IL-12 treatment has opposite effects depending on whether it is administered before or after infection. These results demonstrate the potential risks of immune modulating therapies such as administration of exogenous cytokine or neutralization of cytokine. J. Med. Virol. 88:1487-1496, 2016. © 2016 Wiley Periodicals, Inc.
authors: Department of Microbiology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan.
authors: Hiroki
authors: H
authors: Ishikawa
authors: Department of Microbiology and Immunology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors: Satoshi
authors: S
authors: Ino
authors: Department of Health Science, School of Health and Sports Science, Juntendo University, Inzai, Chiba, Japan.
authors: Hiraku
authors: H
authors: Sasaki
authors: Department of Microbiology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan.
authors: Toshie
authors: T
authors: Fukui
authors: Department of Microbiology and Immunology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors: Chikara
authors: C
authors: Kohda
authors: Department of Microbiology and Immunology, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
authors: Kazuo
authors: K
authors: Tanaka
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004334:Drug Administration Schedule; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007251:Influenza, Human / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control* / Q000821:virology
chemical_list: D016207:Cytokines; D018664:Interleukin-12
keywords: IL-12; NK cell; influenza virus infection; myeloid-derived suppressor cell (MDSC)