Production of tumour necrosis factor by pleural leukocytes following airspace deposition of asbestos, quartz and Ti02, alone and in combination.

Since asbestos exposure may commonly be accompanied by exposure to other non-fibrous particles, we investigated the effects of combinations of crocidolite asbestos with quartz or titanium dioxide (TiO2) in causing bronchoalveolar and pleural leukocyte responses. One month following intratracheal instillation, quartz alone caused a stimulation of leukocytes recruitment to the bronchoalveolar space whilst crocidolite or TiO2 alone did not. A combination of crocidolite and quartz showed a synergistic effect in recruiting leukocytes into the lungs. Pleural leukocytes showed a different response compared to bronchoalveolar leukocytes. When any dust was instilled alone, there was recruitment of pleural leukocytes. The effect of crocidolite plus TiO2 was not different to either dust alone, but crocidolite plus quartz produced an additive effect with respect to cell population. With instillation of dusts alone the pleural leukocytes produced reduced levels of the proinflammatory cytokine, tumour necrosis factor (TNF), compared to controls. However, when the dusts were given in combination, this resulted in a marked increase in TNF production for crocidolite plus TiO2 and an even greater increase with crocidolite plus quartz. In vitro studies showed that alveolar macrophages responded to quartz exposure with an increased secretion of TNF. The combination of asbestos with quartz or TiO2 resulted in raised TNF production by the macrophages. These results indicate that there are different responses in the lungs and the pleura to fibres and fibres plus other dusts. Mixed exposure to asbestos and other mineral dusts result in a dramatic alteration in terms of cell types and TNF secretory activity and this may relate to the increased pleural pathology previously reported for such exposure in the experimental situation.