Distinctive profile of alveolar macrophage-derived cytokine release induced by fibrogenic and nonfibrogenic mineral dusts

Journal of Toxicology and Environmental Health
I Lemaire, S Ouellet

Abstract

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 L...Continue Reading

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