Inflammatory mediators of experimental colitis in rats.
Colonic inflammation was induced in rats by intracolonic administration of 0.25 ml of 50% ethanol containing 30 mg of trinitrobenzene sulfonic acid (TNB). Control rats were treated with 0.25 ml of 50% ethanol or with 30 mg of TNB in 0.25 ml of saline. After 24 h, mucosal ulceration and hemorrhage were observed in TNB/ethanol-, 50% ethanol-, and to a lesser extent, in TNB/saline-treated rats. After 1 wk, mucosal damage was completely resolved in the 50% ethanol and TNB/saline-treated rats but the lesions in the TNB/ethanol-treated rats persisted and progressed to a chronic active inflammatory process after 3 wk. Myeloperoxidase activity was significantly elevated in mucosal scrapings from all treatment groups at all time intervals when macroscopic and microscopic mucosal injury was evident. Interleukin-1 was found to be the most sensitive indicator of mucosal inflammation, and its mucosal values correlated with myeloperoxidase activity. Leukotriene B4 was increased in control rats at 1 wk and in TNB/ethanol-treated rats at all time intervals. The maximal increase in leukotriene B4 was observed at 1 wk. Thromboxane B2 generation was reduced while platelet activating factor generation was not increased in TNB/ethanol-treated rats. These results indicate that in this TNB/ethanol model of gut inflammation, myeloperoxidase activity and interleukin-1 are reliable and sensitive indicators of colonic inflammation, and that thromboxane B2 is not involved in the acute lesions, whereas leukotriene B4 appears in the chronic active inflammatory response.
Rachmilewitz
D
D
Department of Pharmacology, Smith Kline and French Laboratories, King of Prussia, Pennsylvania.
Simon
P L
PL
Schwartz
L W
LW
Griswold
D E
DE
Fondacaro
J D
JD
Wasserman
M A
MA
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism*; D003106:Colon / Q000473:pathology; D000431:Ethanol / Q000633:toxicity; D007375:Interleukin-1 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D007375:Interleukin-1; D010972:Platelet Activating Factor; D007975:Leukotriene B4; D000431:Ethanol; D013929:Thromboxane B2; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase