Reactivation of hapten-induced colitis and its prevention by anti
-inflammatory drugs.
Wallace, John L., Caroline B. Appleyard
Intestinal Disease Research Unit, Faculty of Medicine, University
of Calgary, Calgary, Alberta, T2N 4N1, Canada
APStracts 2:0044G, 1995.
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 man. This
inflammation and injury gradually subsides over the weeks after its
induction. In this study, we have attempted to determine if this
colitis can be $QUOTreactivated$QUOT by administering 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 hour intervals over three days resulted in a
reactivation of the colitis, with significant increases in both
macroscopic and histological damage scores (mucosal injury and
inflammation) and a significant increase in granulocyte infiltration,
as measured by tissue myeloperoxidase activity. The increase in
myeloperoxidase 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
myeloperoxidase activity elicited by intravenous hapten
administration. Cyclosporin A reduced myeloperoxidase activity and 5
-aminosalicylic acid reduced colonic damage score, while lidocaine and
two inhibitors of leukotriene synthesis did not significantly affect
either of these parameters. These results suggest that exposure to an
antigen may result in inflammation at a site in the intestine where
previous damage coupled with exposure to the antigen had occurred.
Received 16 September 1994; accepted in final form 20 February
1995.
APS Manuscript Number G356-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.