Biochemistry and pharmacology of cyclooxygenase inhibitors.

Prostaglandins and leukotrienes are local hormones synthesized from essential fatty acids by the cyclooxygenase and lipoxygenase systems. Many anti-inflammatory drugs function by inhibiting prostaglandin production. Acetylsalicylic acid irreversibly inhibits cyclooxygenase by acetylating a serine residue in the active site. Aspirin selectively stimulates the proliferative responses of T-lymphocytes in part by enhancing IL-2 production. Cells recover from aspirin by synthesizing new cyclooxygenase, and many cells require EGF for this. Corticosteroids block recovery from aspirin treatment by inhibiting synthesis of cyclooxygenase. Cyclooxygenase and lipoxygenase inhibitors frequently have opposing activities. More work on the integration of the prostaglandin and the newly discovered leukotriene systems is needed.