The production of TNF-alpha and IL-1-like activity by bronchoalveolar leucocytes after intratracheal instillation of crocidolite asbestos.

We have used a rat intratracheal instillation model to study the effect of crocidolite asbestos exposure on cytokine production by bronchoalveolar lavage (BAL) leucocytes. In unexposed controls, the normal BAL leucocytes were mostly macrophages which spontaneously produced interleukin 1 (IL-1)-like activity and tumour necrosis factor (TNF-alpha) in culture; these levels were enhanced by stimulation with LPS. In animals exposed to crocidolite asbestos, two new types of cell, neutrophils and eosinophils, were recruited into the bronchoalveolar space by 1-3 days after instillation. However, the BAL profile had returned to normal by 14 days. The production of IL-1-like activity was decreased considerably compared to control from 1 to 14 days after asbestos instillation, but was increased at 30 days. However, the leucocytes produced increased TNF-alpha as early as 3 days after asbestos instillation and maintained this elevated level throughout the experimental period. Crocidolite asbestos in vitro also stimulated normal BAL leucocytes to release significantly increased amounts of IL-1-like activity and TNF-alpha. We conclude that the deposition of crocidolite asbestos fibre in the lung by instillation causes reduced production of IL-1-like activity in the acute phase, but elevated production of both IL-1-like activity and TNF in the chronic phase, suggesting that enhanced activities of these cytokines may contribute to the development of lung pathological changes in the long term.