title: IL-10 regulates viral lung immunopathology during acute respiratory syncytial virus infection in mice.
abstract: Interleukin (IL-) 10 is a pleiotropic cytokine with broad immunosuppressive functions, particularly at mucosal sites such as the intestine and lung. Here we demonstrate that infection of BALB/c mice with respiratory syncytial virus (RSV) induced IL-10 production by CD4(+) and CD8(+) T cells in the airways at later time points (e.g. day 8); a proportion of these cells also co-produced IFN-γ. Furthermore, RSV infection of IL-10(-/-) mice resulted in more severe disease with enhanced weight loss, delayed recovery and greater cell infiltration of the respiratory tract without affecting viral load. In addition, IL-10(-/-) mice had a pronounced airway neutrophilia and heightened levels of pro-inflammatory cytokines and chemokines in the bronchoalveolar lavage fluid. Notably, the proportion of lung T cells producing IFN-γ was enhanced, suggesting that IL-10 may act in an autocrine manner to dampen effector T cell responses. Similar findings were made in mice treated with anti-IL-10R antibody and infected with RSV. Therefore, IL-10 inhibits disease and inflammation in mice infected with RSV, especially during recovery from infection.
authors.affiliation: MRC and Asthma UK Centre, Respiratory Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, United Kingdom.
authors.forename: Jens
authors.initials: J
authors.lastname: Loebbermann
authors.forename: Corinna
authors.initials: C
authors.lastname: Schnoeller
authors.forename: Hannah
authors.initials: H
authors.lastname: Thornton
authors.forename: Lydia
authors.initials: L
authors.lastname: Durant
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Sweeney
authors.forename: Martijn
authors.initials: M
authors.lastname: Schuijs
authors.forename: Anne
authors.initials: A
authors.lastname: O'Garra
authors.forename: Cecilia
authors.initials: C
authors.lastname: Johansson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Openshaw
mesh_terms: D000818:Animals; D018893:Bronchoalveolar Lavage; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism*; D012136:Respiratory Syncytial Viruses / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D016207:Cytokines; D017472:Receptors, Interleukin-1; D016753:Interleukin-10; D007371:Interferon-gamma