Mycophenolate mofetil reduces tissue damage and inflammation in an experimental model of colitis in rats

Background: Lymphocytes are widely believed to be responsible for persisten t intestinal inflammation in inflammatory bower diseases. Mycophenolate mof etil (MMF) is a potent immunosuppressant that inhibits lymphocyte prolifera tion and has been shown to be effective in preventing allograft rejection a fter organ transplantation. The purpose of this study was to assess the mod ulating effects of MNF on intestinal inflammation in an experimental model of colitis in rats. Methods: Colitis was induced by rectal instillation of trinitrobenzenesulfonic acid (TNBS) in ethanol in male Sprague-Dawley rats. One group of rats (n = 10) was treated with MMF i.p. (25 mg/kg b.w.) daily for 1 week starting 24 h after induction of colitis. A second group of rat s (n = 10) was treated with MMF at the same dose 2 days, I day and 1 h prio r to induction of colitis. Control animals (n = 10) received vehicle only. After being killed, colonic tissue was macroscopically evaluated for necros is and microscopically for ulcerations. Sections were stained and examined for the presence of granulocytes. Results: Administration of MMF after indu ction of TNBS colitis reduced macroscopic injury by 62% compared to control animals (P=0.01). Microscopic ulcerations were reduced by 64% compared to controls (P = 0.009). In addition, posttreatment significantly reduced the number of granulocytes. MMF pretreatment did not significantly prevent macr oscopic or microscopic tissue damage, or change the number of granulocytes. Conclusion: Systemic administration of MMF significantly ameliorates tissu e damage in a model of experimental colitis in rats suggesting that this co mpound may play an important role as an immunosuppressant in the therapy of inflammatory bower diseases.