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Selective COX‐2 inhibitors and human inflammatory bowel disease
Author(s) -
Sara McCartney,
Jane A. Mitchell,
Peter D. Fairclough,
M. J. G. Farthing,
Timothy D. Warner
Publication year - 1999
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.1999.00585.x
Subject(s) - medicine , inflammatory bowel disease , ulcerative colitis , gastroenterology , thromboxane , thromboxane b2 , colonoscopy , pharmacology , disease , colorectal cancer , platelet , cancer
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 PGE 2 and PGI 2 , 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 PGE 2 , PGI 2 (measured as 6 keto‐PG F 1α ) and thromboxane (Tx) A 2 (measured as TxB 2 ) determined. Results : Biopsies obtained from diseased colonic mucosa produced significantly more PGE 2 , PGI 2 and thromboxane A 2 than did controls (for example, PGE 2 : 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.