Interleukin-1 (IL-1) is an important cytokine in granulomatous alveolitis.
We examined the role of interleukin-1 (IL-1) in promoting an immune-induced lung fibrotic response in a mouse model of granulomatous alveolitis caused by exposure to heat-killed bacillus Calmette-Guérin. Instillation of the material induced an elevated production of IL-1 in the lungs of challenged mice. Lung homogenates from challenged mice contained high levels of antigenic IL-1, and alveolar macrophages from challenged mice released elevated levels of IL-1. Treatment of mice with a specific monoclonal antibody directed against type-1 IL-1 receptor quite significantly reduced the initial influx of cells, especially neutrophils into the bronchoalveolar lavage. Type-1 IL-1 receptor blockade did not directly alter the levels of tumor necrosis factor alpha in the lung homogenates, but it did lead to an interleukin-6 superinduction in the lungs. IL-1 receptor blockade quite significantly diminished lung tissue damage and granuloma formation, judging from morphometric index and lung hydroxyproline measurements. This diminished tissue damage was also evident on tissue sections stained with Masson's trichrome, as seen by fewer granulomas and less collagen deposition. These data suggest that IL-1 plays an important role in determining a lung granulomatous response.
Pulmonary Research Unit, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
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M
Denis
D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006099:Granuloma / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D017563:Lung Diseases, Interstitial / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000276:immunology
D016207:Cytokines; D007375:Interleukin-1; D017472:Receptors, Interleukin-1