Experimental colitis attenuates development of toxin-induced cholangitis in rats.
Primary sclerosing cholangitis frequently occurs in association with ulcerative colitis. This close association may be due to colitis predisposing patients to bile ductular injury. Therefore, we determined the susceptibility of rats with experimental colitis to toxin-induced cholangitis. Sprague-Dawley rats received 2,4,6-trinitrobenzene-sulfonic-acid (TNBS) or ethanol vehicle intracolonically. Seven days later, rats received either the biliary epithelial cell toxin alpha-naphthylisothiocyanate (ANIT) or vehicle and were killed 24 hr later. Liver histology, serum biochemistries and tumor-necrosis factor-alpha (TNF-alpha), and hepatic interleukin-10 (IL-10) mRNA were determined. TNBS-treated rats showed extensive macroscopic colonic damage and a 10-fold increase in myeloperoxidase activity compared to ethanol-treated controls. ANIT-treated noncolitic rats showed portal inflammation centered on damaged bile ducts (cholangitis), which was markedly attenuated in ANIT-treated colitic rats. Hepatic IL-10 mRNA was twofold higher in colitic compared to noncolitic rats, with no difference in serum TNF-alpha. In conclusion, experimental colitis attenuates the development of toxin-induced cholangitis in rats, possibly by up-regulating hepatic IL-10 expression.
Tjandra
Kartika
K
Liver Unit, University of Calgary, Alberta, Canada.
Le
Tai
T
Swain
Mark G
MG
D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002761:Cholangitis / Q000139:chemically induced / Q000503:physiopathology*; D003093:Colitis, Ulcerative / Q000503:physiopathology*; D004195:Disease Models, Animal; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity; D015854:Up-Regulation
D001647:Bile Acids and Salts; D012333:RNA, Messenger; D016753:Interleukin-10; D014302:Trinitrobenzenesulfonic Acid; D001663:Bilirubin