title: Interleukin-6 in mouse hypersensitivity pneumonitis: changes in lung free cells following depletion of endogenous IL-6 or direct administration of IL-6.
abstract: In this study, we examined the role of interleukin-6 (IL-6) in the development of chronic lung inflammatory conditions, using a mouse model of hypersensitivity pneumonitis established by intranasal instillation of the thermophilic actinomycete Faeni rectivirgula. Challenged mice developed an early neutrophilic response at 24 h, followed by a macrophage/lymphocyte recruitment. The impact of IL-6 on the development of the inflammatory response was assessed by giving infusions of a monoclonal antibody against IL-6 so as to deplete endogenous levels of this cytokine or by giving exogenous IL-6 to challenged mice. Mice challenged intranasally with the actinomycete and given the anti-IL-6 antibody developed a strong, sustained neutrophilic response, with a significantly higher lung free cell number than control mice. Assessment of fibrosis by measuring lung hydroxyproline levels showed that challenged mice given anti-IL-6 developed more significant fibrosis than control mice. Conversely, infusions with IL-6 diminished F. rectivirgula-induced cell recruitments and the fibrotic response in the lungs. Moreover, alveolar macrophages from mice given 2 weeks of F. rectivirgula treatment released high levels of tumor necrosis factor alpha (TNF-alpha) bioactivity upon in vitro lipopolysaccharide challenge, compared to mice instilled with saline only. This TNF-alpha activity produced by macrophages was decreased by in vivo IL-6 treatment and enhanced by in vivo neutralization with anti-IL-6. These observations suggest that IL-6 may play a role in regulating the cellular recruitment in the lungs during an inflammatory response, with dramatic consequences for the cellular profile in the bronchoalveolar lavage and the subsequent fibrosis.
authors.affiliation: Unité de Recherche Pulmonaire, CHUS, Sherbrooke, Quebec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Denis
mesh_terms: D000542:Alveolitis, Extrinsic Allergic / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D005260:Female; D015850:Interleukin-6 / Q000502:physiology*; D008168:Lung / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha