CLINICAL RELEVANCE OF CELLULAR MEDIATORS OF INFLAMMATION IN WORKERS EXPOSED TO ASBESTOS

To identify the clinical relevance of cellular mediators of inflammati on in workers exposed to asbestos, we investigated the relationship be tween inflammatory products primarily released by alveolar macrophages and the clinical expression of asbestos-induced interstitial fibrosis . Our study population consisted of 93 white men who had been occupati onally exposed to asbestos and were on average 60 yr of age. Pulmonary function tests, chest radiographs, high-resolution CT scans, and bron choalveolar lavage (BAL) were performed on almost all study subjects; 11 (11.8%) had restrictive lung function, 22 (23.7%) had abnormal gas exchange, 30 (32.3%) had interstitial fibrosis on chest x-ray, and 24 (25.8%) had interstitial changes on high-resolution CT scan. The cellu lar markers of parenchymal inflammation that we examined included fibr onectin in BAL fluid and alveolar macrophage release of prostaglandin E2 (PGE2), interleukin-1beta (IL-1beta), and tumor necrosis factor (TN F-alpha) under unstimulated and endotoxin (LPS)-stimulated culture con ditions. Significantly higher concentrations of fibronectin in BAL flu id were observed among those with restrictive lung function. In additi on, higher concentrations of PGE2, released from cultured but otherwis e unstimulated alveolar macrophages, were associated with restrictive lung function. However, the inverse relationship with PGE2 was observe d among subjects with abnormal gas exchange. Interestingly, no consist ent changes in these inflammatory mediators were observed in those wit h interstitial changes identified on either the chest radiograph or th e high-resolution CT scan. Moreover, the concentration of IL-1beta and TNF-alpha released by alveolar macrophages under either unstimulated or LPS-stimulated culture conditions were not significantly related to the physiologic or radiographic expression of asbestos-induced inters titial fibrosis. In aggregate, our results suggest that among workers exposed to asbestos, cell products primarily derived from alveolar mac rophages do not appear to be associated with mild radiographic manifes tations of asbestos-induced interstitial lung disease. However, higher concentrations of fibronectin and PGE2 released from cultured alveola r macrophages appear to be associated with restrictive lung function.