Distinctive profile of alveolar macrophage-derived cytokine release induced by fibrogenic and nonfibrogenic mineral dusts.
Groups of 7 Wistar rats each received a single intratracheal instillation of either saline (control), UICC chrysotile B asbestos (5 mg), or very short 4T30 chrysotile asbestos fibers (5 mg). Five animals in each group were killed at 1, 3, and 6 wk posttreatment and analyzed by bronchoalveolar lavage (BAL) for BAL cell populations and cytokine production in conjunction with histopathological assessment of lung tissue. Chrysotile B and short 4T30 chrysotile fibers induced chronic inflammatory reactions characterized by alveolar macrophage (AM) accumulation that resulted, respectively, in lung fibrosis and resolving granuloma. Alveolar macrophages (AM) obtained from rats treated with UICC chrysotile B and short 4T30 chrysotile produced enhanced levels of interleukin-1 (IL-1) and interleukin-6 (IL-6), both spontaneously and in response to lipopolysaccharide (LPS). A different pattern of response was observed for tumor necrosis factor-alpha (TNF-alpha). Fibrogenic chrysotile B caused biphasic changes characterized by significant inhibition of LPS-induced TNF-alpha release by AM 1 and 3 wk after treatment, followed by stimulation of spontaneous and LPS-induced TNF-alpha at 6 wk. In contrast, no significant change in spontaneous and LPS-induced TNF-alpha release was seen with AM from animals with resolving granuloma (4T30 group). Thus, modulation of AM-derived TNF-alpha was correlated under these conditions with the fibrogenic potential of asbestos dusts. These data support a role for TNF-alpha in fibrosis and suggest that TNF-alpha may represent a useful marker of lung damage induced by fibrogenic dusts.
Lemaire
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Laboratory of Immunopharmacology, Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Ouellet
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D000818:Animals; D017632:Asbestos, Serpentine / Q000008:administration & dosage / Q000633:toxicity*; D018893:Bronchoalveolar Lavage; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004391:Dust / Q000009:adverse effects*; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D007442:Intubation, Intratracheal; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D019016:Mineral Fibers / Q000633:toxicity; D011658:Pulmonary Fibrosis / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D017632:Asbestos, Serpentine; D016207:Cytokines; D004391:Dust; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D019016:Mineral Fibers; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha