Eicosanoid production by human monocytes: does COX-2 contribute to a self-limiting inflammatory response?

The eicosanoids, prostaglandin E-2 (PGE(2)) and thromboxane A(2) (TXA(2)), are involved in inflammatory events. TXA(2) has potentially pro-inflammator y actions and PGE(2) has actions which can be considered both pro- and anti -inflammatory. Therefore, it is potentially significant that production of TXA(2) and PGE(2) by stimulated monocytes have very different time courses. TXA(2) synthesis is immediate and dependent on cyclooxygenase Type 1 (COX- 1) activity whereas PGE(2) synthesis is delayed and dependent on COX-2 acti vity. These apparent COX-isotype dependencies of TXA(2), and PGE(2) synthes is can be explained by differences in the affinities of TXA synthase and PG E synthase for the common substrate, PGH(2). The findings have implications for the use of NSAIDs and selective COX-2 inhibitors whose actions can inc rease the monocyte TXA(2)/PGE(2) ratio.