Reactivation of hapten-induced colitis and its prevention by anti-inflammatory drugs.
Administration of a hapten together with a barrier breaker, such as ethanol, into the colon of a rat results in extensive mucosal injury and inflammation that bears some similarity to the colonic inflammation characterizing inflammatory bowel disease in humans. This inflammation and injury gradually subsides over the weeks after its induction. We have attempted to determine whether this colitis can be "reactivated" by administration of the hapten systemically weeks after its initial intracolonic administration. Six weeks after intracolonic administration of trinitrobenzene sulfonic acid (the hapten) in a vehicle of 50% ethanol, most of the colonic injury and inflammation had subsided. Intravenous administration of the hapten at 24-h intervals over 3 days resulted in reactivation of the colitis, with significant increases in macroscopic and histological damage scores (mucosal injury and inflammation) and a significant increase in granulocyte infiltration, as measured by tissue myeloperoxidase (MPO) infiltration, as measured by tissue myeloperoxidase (MPO) activity. The increase in MPO activity occurred only in the region previously exposed to the hapten. Intravenous administration of saline did not reactivate the colitis, nor did intravenous administration of the hapten to rats previously treated intracolonically with saline or the ethanol vehicle. Reactivation of colitis by hapten administration was not accompanied by activation of mucosal mast cells. Treatment with dexamethasone prevented the increase in colonic damage score and MPO activity elicited by intravenous hapten administration. Cyclosporin A reduced MPO activity, and 5-aminosalicylic acid reduced the colonic damage score, whereas lidocaine and two inhibitors of leukotriene synthesis did not significantly affect either of these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
Appleyard
C B
CB
Intestinal Disease Research Unit, Faculty of Medicine, University of Calgary, Alberto, Canada.
Wallace
J L
JL
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D053818:Chymases; D003092:Colitis / Q000139:chemically induced* / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000201:enzymology; D006241:Haptens; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence; D012697:Serine Endopeptidases / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid
D000893:Anti-Inflammatory Agents; D006241:Haptens; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D012697:Serine Endopeptidases; D053818:Chymases