Endothelin-stimulated human monocytes produce prostaglandin E2 but not leukotriene B4

The activation and proliferation of a prostaglandin E2 (PGE2) producing monocyte/macrophage may play a major role in down-regulating immune function after injury. But the mechanism by which monocyte or macrophage activation occurs in injury is unknown. Endothelin is a 21-amino acid peptide produced by vascular endothelium in response to ischemia, injury, or endotoxin. Prior work from our laboratory has shown that endothelin increases intracellular calcium in monocytes and causes production of interleukins-6 and -8. In the data reported in this paper, 10(-9) M endothelin stimulated human monocytes to produce 1050 +/- 63 pg/ml of PGE2 at 6 hr and 1328 +/- 47 pg/ml at 24 hr. This was nearly as much PGE2 production as that by bacterial lipopolysaccharide (endotoxin) stimulation (1295 +/- 47 pg/ml at 6 hr and 1506 +/- 94 at 24 hr). Endothelin had no effect on production of leukotriene B4. Endothelin may play an important initiating role in post-traumatic immunosuppression.