Eicosanoid And Cytokine Production By The Alveolar Macrophage From The Coal Miner

Eicosanoids and cytokines produced by the alveolar macrophage (AM) are key mediators of pulmonary inflammation and fibrosis resulting from occupational exposure to mineral dust. In order to determine if eicosanoid and cytokine production are altered by chronic inhalation of coal dust, we compared the production of prostaglandin E2 (PGE2), thromboxane A2 (TxA2), leukotriene B4 (LTB4), interleukin 1 (IL-1), tumor necrosis factor (TNF) and platelet-derived growth factor (PDGF) by cultured AM from non-smoking normal human volunteers and coal miners. Inhibitors of eicosanoid biosynthesis were administered to AM from coal miners in order to determine if a link between eicosanoid and cytokine production exists in these cells. Basal PGE2, TxA2, TNF and IL-1 production by AM from active miners was increased compared to AM from normal volunteers. However, the production of these eicosanoids and cytokines by AM from former coal miners was reduced compared to control AM. Administration of the cyclooxygenase inhibitor, suprofen, and the lipoxygenase inhibitor, nordihydroguaiaretic acid, reduced PGE2 and TxA2 production in miners' AM but had no effect on LTB4, IL-1 or PDGF production. Specific inhibition of thromboxane synthase by UK38,485 was associated with a significant reduction in TNF production in active miners' AM but had no effect on PGE2, LTB4 or IL-1 production. The prostacyclin analogue ZK96,480 also specifically inhibited TxA2 production in active miners' AM. The results of these studies suggest that coal dust exposure is associated with alterations in AM eicosanoid and cytokine production which may be relevant to the development of pulmonary inflammation and fibrosis. In addition, the lack of effect of inhibitors of PGE2 biosynthesis on IL1 production in miners' AM suggests the production of these intercellular messengers may not be linked in AM chronically exposed to coal dust.