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Effects of a COX-2 Preferential Agent Nimesulide on TNBS-Induced Acute Inflammation in the Gut

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Abstract

In inflammatory bowel disease, increased production of prostaglandins by cyclooxy- genase-2 (COX-2) contributes to bowel dysfunction, inflammatory edema, and hyperemia suggesting that inhibitors of COX-2 may have beneficial effect in gut inflammation. We compared the effects of nimesulide, a preferential COX-2 inhibitor, with those of indomethacin, acetylsalicylic acid (ASA), and dexamethasone in a 24-h model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in the rat. TNBS-induced colitis was associated with enhanced COX-2 expression in the gut and increased circulating concentrations of PGE2 metabolite (PGEM). Treatment with nimesulide (10 mg/kg), indomethacin (10 mg/kg), or dexamethasone (1 mg/kg) reduced plasma PGEM concentrations and edema in the inflamed bowel. In addition, nimesulide and dexamethasone treatments decreased neutrophil infiltration into the inflamed colon mucosa. ASA (10 mg/kg) did not have a significant effect on any of these measures of inflammation. None of the studied drugs reduced the size of inflammatory mucosal lesions in the colon. In TNBS-induced acute inflammation of the colon, nimesulide reduced the formation of inflammatory edema, probably by a mechanism related to inhibition of PGE2 production by COX-2 pathway. In addition, nimesulide inhibited neutrophil infiltration into inflamed mucosa mimicking the action of dexamethasone.

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Authors and Affiliations

  1. Institute of Biomedicine, Pharmacology, University of Helsinki, Biomedicum, Helsinki, Finland

    Esko Kankuri, Kirsi Vaali, Riitta Korpela, Ilari Paakkari & Heikki Vapaatalo

  2. The Immunopharmacological Research Group, Medical School, University of Tampere and Tampere University Hospital, Tampere, Finland

    Eeva Moilanen

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Kankuri, E., Vaali, K., Korpela, R. et al. Effects of a COX-2 Preferential Agent Nimesulide on TNBS-Induced Acute Inflammation in the Gut. Inflammation 25, 301–310 (2001). https://doi.org/10.1023/A:1012860509440

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