Overview of COX-2 in inflammation: from the biology to the clinic

Abstract

Cyclooxygenase (COX) is part of a bifunctional enzyme, prostaglandin H synthase (PGHS), which catalyzes the first step in the conversion of membrane phospholipids (principally, arachidonic acid) into prostanoids (prostaglandins and thromboxanes). Prostanoids contribute to diverse physiological and pathological processes including inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs), the prototype of which is aspirin, owe their therapeutic effects to blockade of prostaglandin synthesis through COX blockade [1]. NSAIDs are a heterogenous group of compounds, often chemically unrelated, which nevertheless share therapeutic effects (i.e. antiinflammatory, analgesic and antipyretic) and side effects (i.e. gastrointestinal erosions, decreased renal function, inhibition of platelet aggregation). Until recently, it had been widely accepted that a common mechanism (COX inhibition) is responsible for both the therapeutic and the side-effects of NSAIDs. However, this theory has been refined since the discovery of a second, inducible COX isozyme, COX-2 [2, 3]. It has been proposed that COX-2 inhibition is relevant for the anti-inflammatory effects of NSAIDs, whereas inhibition of constitutive COX-1 is responsible for the gastric and renal side effects, as well as for the antithrombotic activity of these agents [4].