Eicosanoid and cytokine production by the pulmonary alveolar macrophage.
Demers LM; Kuhn DC; Gaydos L; Stauffer JL
Eicosanoids and other bioactive lipids in cancer, inflammation, and radiation injury: proceedings of the 2nd International Conference September 17-21, 1991 Berlin, FRG (Developments in Oncology). Nigam S, Honn KV, Marnett LJ, Walden TL Jr., eds. New York: Kluwer Academic Publishers, 1993 Jan; 4:497-502
Eicosanoids and cytokines produced by the pulmonary alveolar macrophage (PAM) are key mediators for the defensive role this cell plays in neutralizing the inhalation of pariculate dusts and foreign microbes. However, these factors are also mediators of inflammation and their uncontrolled release may cause the lung injury and fibrotic changes observed in individuals exposed occupationally to mineral dust. In vitro studies have suggested a link between the production of certain eicosanoids and cytokines released from the activated PAM. To this end, we have studied the release of eicosanoids (PGE2, TXB2 and LTB4) and cytokines (IL-1 and TNF) by cultured PAM, obtained from healthy human volunteers by bronchoalveolar lavage under basal culture conditions and following acute exposure to provocative agents such as the endotoxin lipopolysaccharide (LPS) and mineral dusts including silica. Studies were also carried out in the presence of specific cyclooxygenase inhibitors. The addition of LPS (10 ug/ml) to the culture medium produced a significant increase in PAM release of the eicosanoids: PGE2 (3.5 fold over baseline), TXB2 (2.8 fold over baseline) and LTB4 (4 fold over baseline). LPS also elicited a 2.5 fold elevation in IL-1 from these cells and a 9 fold increase in TNF release. The cyclooxygenase inhibitor, ibuprofen, significantly inhibited the LPS-induced rise in PGE2, TXB2 and TNF but had only a modest suppressive effect on IL-1 release. Exposure of these cells to silica dust elicited a similar augmentation in eicosanoid and cytokine release which was neutralized by prior exposure of the cells to ibuprofen. These results suggest that the enhanced production of eicosanoids and cytokines by PAM exposed to endotoxins and/or mineral dusts may be linked and that inhibition of eicosanoid release is linked to the production of TNF. IL-1 release however is not effectively neutralized by cyclooxygenase inhibition.
health and safety; lung disease; respirable dust;
Author Keywords: Tumor Necrosis Factor; Mineral Dust; Cyclooxygenase Inhibitor; Silica Dust; Silica Exposure
Nigam S; Honn KV; Marnett LJ; Walden TL Jr.
Eicosanoids and other bioactive lipids in cancer, inflammation, and radiation injury 4
Pennsylvania State University