Mycophenolate mofetil reduces tissue damage and inflammation in an experimental model of colitis in rats.
BACKGROUND
Lymphocytes are widely believed to be responsible for persistent intestinal inflammation in inflammatory bowel diseases. Mycophenolate mofetil (MMF) is a potent immunosuppressant that inhibits lymphocyte proliferation and has been shown to be effective in preventing allograft rejection after organ transplantation. The purpose of this study was to assess the modulating effects of MMF 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 rats (n = 10) was treated with MMF at the same dose 2 days, I day and 1 h prior to induction of colitis. Control animals (n = 10) received vehicle only. After being killed, colonic tissue was macroscopically evaluated for necrosis and microscopically for ulcerations. Sections were stained and examined for the presence of granulocytes.


RESULTS
Administration of MMF after induction 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 macroscopic or microscopic tissue damage, or change the number of granulocytes.


CONCLUSIONS
Systemic administration of MMF significantly ameliorates tissue damage in a model of experimental colitis in rats suggesting that this compound may play an important role as an immunosuppressant in the therapy of inflammatory bowel diseases.
Zeeh
J M
JM
Dept of Internal Medicine, University of Essen, Germany. joerg.zeeh@uni-essen.de
Zorlu
Riley
N E
NE
Hoffmann
P
P
Ruwe
M
M
Goebell
H
H
Gerken
G
G
Dignass
A U
AU
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000473:pathology; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid
D007166:Immunosuppressive Agents; D014302:Trinitrobenzenesulfonic Acid; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid