Arachidonic acid metabolism as a source of inflammatory mediators and its inhibition as a mechanism of action for anti-inflammatory drugs

Arachidonic acid is released by the action of phospholipase and can be oxygenated by two known pathways. Cyclo-oxygenase is present in every tissue and is activated whenever tissues are damaged or stimulated. Cyclo-oxygenase products are powerful mediators of inflammatory erythema, oedema and hyperalgesia. The lipoxygenase product 5,12-DHETE (Leukotriene B) is a potent chemotactic factor for polymorphonuclear leukocytes and it could play an important role in the endogenous control of leukocyte function. Other leukotriene products of arachidonate lipoxygenase are mediators of immediate hypersensitivity. Non-steroid anti-inflammatory drugs such as indomethacin and the salicylates are selective cyclo-oxygenase inhibitors and they may even enhance lipoxygenase activity by diversion of substrate. The improved anti-inflammatory activity of corticosteroids is probably accounted for by interference with phospholipase action which indirectly results in an inhibition of both cyclo-oxygenase and lipoxygenase activity. There is evidence that dual inhibitors of arachidonic acid oxygenation may have advantages over selective cyclo-oxygenase inhibitors or steroids in the treatment of chronic inflammation and anaphylactic broncho-constriction.