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

The eicosanoids, prostaglandin E₂ (PGE₂) and thromboxane A₂ (TXA₂), are involved in inflammatory events. TXA₂ has potentially pro-inflammatory actions and PGE₂ has actions which can be considered both pro- and anti-inflammatory. Therefore, it is potentially significant that production of TXA₂ and PGE₂ by stimulated monocytes have very different time courses. TXA₂ synthesis is immediate and dependent on cyclooxygenase Type 1 (COX-1) activity whereas PGE₂ synthesis is delayed and dependent on COX-2 activity. These apparent COX-isotype dependencies of TXA₂ and PGE₂ synthesis can be explained by differences in the affinities of TXA synthase and PGE synthase for the common substrate, PGH₂. The findings have implications for the use of NSAIDs and selective COX-2 inhibitors whose actions can increase the monocyte TXA₂/PGE₂ ratio.