Selective COX‐2 inhibitors and human inflammatory bowel disease

• Published in: Alimentary pharmacology & therapeutics Vol. 13; no. 8; pp. 1115 - 1117
• Main Authors: MCCARTNEY, S. A, MITCHELL, J. A, FAIRCLOUGH, P. D, FARTHING, M. J. G, WARNER, T. D
• Format: Journal Article
• Language: English
• Published: Oxford UK Blackwell Science Ltd 01.08.1999; Blackwell
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Colitis, Ulcerative - metabolism; Colitis, Ulcerative - pathology; Crohn Disease - metabolism; Crohn Disease - pathology; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Humans; In Vitro Techniques; Indans - adverse effects; Indomethacin - adverse effects; Inflammatory Bowel Diseases - metabolism; Inflammatory Bowel Diseases - pathology; Isoenzymes - metabolism; Medical sciences; Membrane Proteins; Pharmacology. Drug treatments; Prostaglandin-Endoperoxide Synthases - metabolism; Prostaglandins - metabolism; Human; Prostaglandin-endoperoxide synthase; Prostaglandin I2; Digestive system; Enzyme; Isozyme; Thromboxane A2; Indometacin; Enzyme inhibitor; Prostaglandin E2; In vitro; Inflammatory disease; Non steroidal antiinflammatory agent; Crohn disease; Prostanoid; Indoleacetic acid derivatives; Digestive diseases; Intestinal disease; Oxidoreductases; Colon; Ulcerative colitis
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1046/j.1365-2036.1999.00585.x

Background : Much recent effort has been made to produce selective inhibitors of cyclo‐oxygenase‐2 (COX‐2) in the belief that these will lack the gastrointestinal damaging effects of traditional non‐steroidal anti‐inflammatory drugs (NSAIDs). Inflammatory bowel disease is associated with increased local production of prostanoids. These prostanoids, particularly PGE2 and PGI2, may well be protective as inflammatory bowel disease is aggravated by NSAID use. Aim : To examine the effects of a traditional NSAID and a highly selective COX‐2 inhibitor on the production of these prostanoids in human inflammatory bowel disease. Methods : Colonic mucosal biopsies were obtained from patients undergoing routine colonoscopy and biopsy for diagnostic or surveillance purposes. Biopsies were incubated in culture medium containing 10% foetal calf serum and antibiotics, plus test drugs or vehicle for 24 h, after which time the medium was removed and the content of PGE2, PGI2 (measured as 6 keto‐PGF1α) and thromboxane (Tx) A2 (measured as TxB2) determined. Results : Biopsies obtained from diseased colonic mucosa produced significantly more PGE2, PGI2 and thromboxane A2 than did controls (for example, PGE2: ulcerative colitis, 4.17 ± 1.06; Crohn’s disease, 3.97 ± 1.66; control, 0.12 ± 0.13 ng/mL, n=8–12). These increases were inhibited to a similar extent by either a highly selective COX‐2 inhibitor (L‐745 337) or a traditional non‐selective NSAID (indomethacin). Conclusions : Until selective COX‐2 inhibitors have been assessed adequately in human inflammatory bowel disease, these compounds should not be assumed to be safe for the gastrointestinal tract in inflammatory bowel disease.