Granulocyte infiltration in experimental colitis in the rat is interleukin-1 dependent and leukotriene independent.
Intracolonic administration of trinitrobenzene sulfonic acid in ethanol results in the development of colitis in the rat. Previous studies have demonstrated that the severity of this colitis can be markedly reduced by repeated treatment with inhibitors of leukotriene synthesis, although such treatment does not appear to affect the initial migration of granulocytes into the colon. The present study evaluated the contribution of leukotrienes and interleukin-1 to the recruitment of granulocytes into the colon during the first 12 h after induction of colitis. Rats were treated with a leukotriene synthesis inhibitor (PF-5901), a leukotriene B4 receptor antagonist (SC-41930), an IL-1 receptor antagonist or a corticosteroid (prednisolone) prior to induction of colitis. Granulocyte infiltration was assessed by measurement of colonic myeloperoxidase activity and severity of colonic damage was blindly scored. Despite significant inhibition of leukotriene synthesis, PF-5901 did not affect colonic myeloperoxidase activity or the severity of colonic injury at any time point. Similarly, SC-41930 was without significant effect. However, both the interleukin-1 receptor antagonist and prednisolone significantly reduced colonic myeloperoxidase activity (by approximately 50%) and severity of colonic damage at 6 h after induction of colitis, without significantly affecting colonic leukotriene synthesis. These beneficial effects were no longer apparent at 12 h after induction of colitis. This study demonstrates that the infiltration of granulocytes into the colon during the acute phase of colitis in the rat occurs independent of leukotriene synthesis and appears to be at least in part attributable to interleukin-1.
McCafferty
D M
DM
Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
Rioux
K J
KJ
Wallace
J L
JL
D000704:Analysis of Variance; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte; D003092:Colitis / Q000276:immunology* / Q000503:physiopathology; D007375:Interleukin-1 / Q000378:metabolism*; D007700:Kinetics; D007975:Leukotriene B4 / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid / Q000378:metabolism
D001578:Benzopyrans; D007375:Interleukin-1; D011804:Quinolines; C049740:alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol; C059950:SC 41930; D007975:Leukotriene B4; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase