title: IL-18 induces airway hyperresponsiveness and pulmonary inflammation via CD4+ T cell and IL-13.
abstract: IL-18 plays a key role in the pathogenesis of pulmonary inflammatory diseases including pulmonary infection, pulmonary fibrosis, lung injury and chronic obstructive pulmonary disease (COPD). However, it is unknown whether IL-18 plays any role in the pathogenesis of asthma. We hypothesized that overexpression of mature IL-18 protein in the lungs may exacerbate disease activities of asthma. We established lung-specific IL-18 transgenic mice on a Balb/c genetic background. Female mice sensitized- and challenged- with antigen (ovalbumin) were used as a mouse asthma model. Pulmonary inflammation and emphysema were not observed in the lungs of naïve transgenic mice. However, airway hyperresponsiveness and airway inflammatory cells accompanied with CD4(+) T cells, CD8(+) T cells, eosinophils, neutrophils, and macrophages were significantly increased in ovalbumin-sensitized and challenged transgenic mice, as compared to wild type Balb/c mice. We also demonstrate that IL-18 induces IFN-γ, IL-13, and eotaxin in the lungs of ovalbumin-sensitized and challenged transgenic mice along with an increase in IL-13 producing CD4(+) T cells. Treatment with anti-CD4 monoclonal antibody or deletion of the IL-13 gene improves ovalbumin-induced airway hyperresponsiveness and reduces airway inflammatory cells in transgenic mice. Overexpressing the IL-18 protein in the lungs induces type 1 and type 2 cytokines and airway inflammation, and results in increasing airway hyperresponsiveness via CD4(+) T cells and IL-13 in asthma.
authors: Division of Respirology, Neurology and Rheumatology, Department of Medicine 1, Kurume University School of Medicine, Fukuoka, Japan.
authors: Masanori
authors: M
authors: Sawada
authors: Tomotaka
authors: T
authors: Kawayama
authors: Haruki
authors: H
authors: Imaoka
authors: Yuki
authors: Y
authors: Sakazaki
authors: Hanako
authors: H
authors: Oda
authors: Shin-ichi
authors: S
authors: Takenaka
authors: Yoichiro
authors: Y
authors: Kaku
authors: Koichi
authors: K
authors: Azuma
authors: Morihiro
authors: M
authors: Tajiri
authors: Nobutaka
authors: N
authors: Edakuni
authors: Masaki
authors: M
authors: Okamoto
authors: Seiya
authors: S
authors: Kato
authors: Tomoaki
authors: T
authors: Hoshino
mesh_terms: D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D007073:Immunoglobulin E / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D020382:Interleukin-18 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000209:etiology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D018793:Interleukin-13; D020382:Interleukin-18; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin
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