COX-1, COX-2, and COX-3 and the future treatment of chronic inflammatory disease

• Published in: The Lancet (British edition) Vol. 355; no. 9204; pp. 646 - 648
• Main Authors: Willoughby, Derek A, Moore, Adrian R, Colville-Nash, Paul R
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 19.02.2000; Lancet; Elsevier Limited
• Subjects: Animals; Anti-inflammatory agents; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - therapeutic use; Drug therapy; Enzymes; Humans; Inflammation - drug therapy; Isoenzymes - pharmacology; Medical sciences; Membrane Proteins; Nonsteroidal anti-inflammatory drugs; Peroxidases - antagonists & inhibitors; Pharmacology. Drug treatments; Prescription drugs; Prostaglandin-Endoperoxide Synthases - chemistry; Prostaglandin-Endoperoxide Synthases - pharmacology; Protein Isoforms; Human; Prostaglandin-endoperoxide synthase; Enzyme; Indication; Treatment efficiency; Antiinflammatory agent; Pharmacology; Inflammation; Gastrointestinal; Non steroidal antiinflammatory agent; Prevention; Chemotherapy; Chronic; Perspective; Secondary effect; Digestive diseases; Oxidoreductases; Pharmacokinetics
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(99)12031-2

A new generation of non-steroidal anti-inflammatory drugs has been described that selectively targets the inducible isoform of cyclo-oxygenase, cyclo-oxygenase 2 (COX-2). This isoform is expressed at sites of inflammation, which has led to the speculation that its inhibition could provide all the benefits of current nonsteroidal anti-inflammatory drugs, but without their major side-effects on the gastrointestinal system (which are due to inhibition of COX-1). We have shown that COX-2 (identified by use of specific antibodies) is induced during the resolution of an inflammatory response, inhibition of COX-2 resulting in persistence of the inflammation due to the prevention of the synthesis of a range of anti-inflammatory prostanoids. We propose that there is a third isoform of this enzyme family, COX-3, a proposal that will have implication for the prescription of both existing and new generation anti-inflammatory drugs, and might represent a new therapeutic target.