EPIDEMIOLOGIC EVALUATION OF RELEASE OF MONOCYTE TNF-ALPHA AS AN EXPOSURE AND EFFECT MARKER IN PNEUMONOCONIOSIS - A 5-YEAR FOLLOW-UP-STUDY OF COAL-WORKERS

Objectives-To determine (a) reproducibility with previous cross sectio nal findings, and (b) the predictive value of initial release of tumou r necrosis factor-alpha (TNF-alpha) towards later progression of coalw orkers' pneumoconiosis (CWP). Methods-Release of monocyte TNF-alpha af ter in vitro stimulation with coal mine dust, silica, and endotoxin wa s measured in 104 retired miners and was related to stage of CWP (ches t radiograph) and cumulative exposure. A subgroup of 46 miners was scr eened by high resolution computed tomography (HRCT). Prospective analy sis of TNF-alpha (40 out of 104 miners involved in the previous TNF-al pha study) was done by relating initial TNF- to five year progression of CWP measured by comparison of paired chest radiographs. Results-As observed previously, dust stimulated release of TNF-alpha was increase d in miners, especially in the early stages of pneumoconiosis. Cumulat ive exposure was related to pneumoconiotic stage but not to release of TNF-alpha. This excluded TNF-alpha as an exposure marker. Initial con centrations (1987) of TNF-alpha were related to later progression of C WP. Miners who showed abnormally high dust stimulated release of TNF-a lpha had an increased risk of progression in CWP (relative risk 8.1). Conclusions-These results show (a) the significant involvement of TNF- alpha in pneumoconiosis in humans induced by coal dust and (b) that th is routine test possibly constitutes a powerful tool to estimate indiv idual prognosis of pneumoconiotic disease, even after the end of occup ational exposure.