Effects of acetaminophen on constitutive and inducible prostanoid biosynthesis in human blood cells

Acetaminophen, an analgesic and antipyretic drug with weak antiinflammatory properties, has been suggested to act as a tissue‐selective inhibitor of prostaglandin H synthases (PGHSs) (e.g. COX‐1 and COX‐2) through its reducing activity, that is influenced by the different cellular levels of peroxides. We have studied the effects of acetaminophen on inducible and constitutive prostanoid biosynthesis in monocytes and platelets in vitro. To discriminate between the inhibitory effect of the drug on PGHS‐isozymes vs PGE‐synthases (PGESs), parallel measurements of PGE2 and thromboxane (TX) B2 were carried out. Since antioxidant enzymes and cofactors, present in plasma, may affect acetaminophen‐dependent inhibition of prostanoids, comparative experiments in whole blood vs isolated monocytes were performed. Acetaminophen inhibited LPS‐induced whole blood PGE2 and TXB2 production, in a concentration‐dependent fashion [IC50 μM (95% confidence intervals): 44 (27–70) and 94 (79–112), respectively]. Therapeutic plasma concentrations (100 and 300 μM) of the drug more profoundly reduced PGE2 than TXB2 (71±3 vs 54±4 and 95±0.8 vs 78±2%, respectively, mean±s.e.mean, n=6, P