Participation of thromboxane and other eicosanoid synthesis in the course of experimental inflammatory colitis.

Eicosanoids, as modulators of inflammation, may be involved in the pathogenesis of inflammatory bowel disease. We investigated their potential role in a rat model of chronic granulomatous colonic inflammation induced by trinitrobenzene sulphonic acid. Luminal eicosanoid release was quantified in vivo using a dialysis bag placed into the distal colon. We tested the effect of drugs known to modify inflammatory activity or arachidonic acid metabolism. Three days after intracolonic injection of trinitrobenzene sulphonic acid at different dose levels, the dialysates showed a highly significant increase of prostaglandin E2, 6-keto-prostaglandin F1 alpha, thromboxane B2 (TXB2), and leukotriene B4, compared with levels in controls not subjected to the toxic agent. Remarkably, the release of TXB2 continued to increase during the stage of chronic inflammation (up to day 21), whereas the levels of the remainder eicosanoids declined. Treatment with prednisone or 5-aminosalicylic acid reduced TXB2 levels in the chronic stage of the inflammatory disease and improved the morphological damage as assessed macroscopically and histologically. Moreover, two selective thromboxane synthetase inhibitors, OKY 1581 and R70416, significantly reduced the development of chronic inflammatory lesions in the colon while inhibiting the release of TXB2. Our results indicate that (1) luminal release of thromboxane increases in the chronic stage of colonic inflammation, (2) anti-inflammatory treatment reduces tissue damage and thromboxane release, and (3) selective thromboxane synthetase inhibition improves the course of the disease in our experimental model.