title: IL-6 induced by double-stranded RNA augments allergic inflammation via suppression of Foxp3+ T-cell/IL-10 axis.
abstract: Activation of innate immunity against viruses in the respiratory tracts affects the development of asthma. Most respiratory viruses generate double-stranded (ds)RNA during their replication. We recently showed that a low-dose administration of polyinosinic polycytidylic acid (poly IC), a mimetic of viral dsRNA, during allergen sensitization augments airway eosinophilia and hyperresponsiveness in mice via enhanced production of IL-13 from T cells. However, a phenotype of asthma under severer load of dsRNA remains unknown. d-galactosamine (d-GalN) is known as a strong sensitizer of poly IC. Mice were treated with poly IC plus d-GalN during allergen sensitization. A sublethal dose of poly IC/d-GalN augmented airway eosinophilia and CD4(+) T-cell accumulation in the lungs but not airway hyperresponsiveness. The augmented inflammation was associated with decreased IL-10 in the bronchoalveolar lavage fluid and decreased Foxp3(+) regulatory T cells in the lungs. Serum IL-6 was prominently higher in the mice treated with poly IC/d-GalN than in that with poly IC alone or d-GalN alone. Poly IC/d-GalN did not affect IL-17-producing T cells in the lungs. Poly IC/d-GalN failed to augment airway eosinophilia after anti-IL-10 receptor monoclonal antibody treatment during allergen challenge. Finally, anti-IL-6 receptor monoclonal antibody treatment before poly IC/d-GalN completely prevented the decrease of IL-10 and Foxp3(+) regulatory T cells and the augmentation of airway inflammation. These results indicate that enhanced production of IL-6 by poly IC/d-GalN induces the augmentation of allergic inflammation via suppression of Foxp3(+) regulatory T-cell/IL-10 axis. IL-6 may be a target for preventing asthma augmentation related to severe virus infection.
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan. koichi@kokyu.med.kyushu-u.ac.jp
authors.forename: Koichiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Yukari
authors.initials: Y
authors.lastname: Asai
authors.forename: Satoru
authors.initials: S
authors.lastname: Fukuyama
authors.forename: Keiko
authors.initials: K
authors.lastname: Kan-O
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: Naotaka
authors.initials: N
authors.lastname: Noda
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kitajima
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Inoue
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D012330:RNA, Double-Stranded / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015850:Interleukin-6; D012330:RNA, Double-Stranded; D016753:Interleukin-10