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Interleukin‐6 in mouse hypersensitivity pneumonitis: changes in lung free cells following depletion of endogenous IL‐6 or direct administration of IL‐6
Author(s) -
Denis Michel
Publication year - 1992
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.52.2.197
Subject(s) - cytokine , biology , immunology , tumor necrosis factor alpha , hypersensitivity pneumonitis , in vivo , lipopolysaccharide , lung , medicine , microbiology and biotechnology
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 in‐tranasally 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–induccd 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 a (TNF‐α) bioactivity upon in vitro lipopolysaccharide challenge, compared to mice instilled with saline only. This TNF‐α 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.