Article: article from journal or magazin.
Long-term evaluation of a rat model of chronic cholangitis resembling human primary sclerosing cholangitis.
Scandinavian Journal of Immunology
Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder with a presumed autoimmune aetiopathogenesis. We have recently described a novel organ-specific rat model of fibrosing cholangitis induced by intrabiliary administration of the hapten-reagent 2,4,6-trinitrobenzenesulfonic acid (TNBS) with similarities to human PSC. In the present report, we have evaluated the long-term outcome of TNBS-induced cholangitis in this model. Mild stenosis of the common bile duct of female Lewis rats (n = 18) was achieved by subtotal ligation and cholangitis induced by TNBS injection (50 mg/kg) into the dilated bile duct after a second laparotomy. After 8 and 12 months, we found no evidence of cholangitis in serum chemistry or histology or retrograde cholangiography of TNBS-treated rats. Antineutrophil cytoplasmic antibodies were positive in 75% of animals but were not predictive of liver damage. Tumour necrosis factor-alpha levels were not elevated in serum or in mononuclear spleen cell supernatants. Our findings suggest that a single initial insult is not sufficient to trigger chronic progressive inflammation. Rather, perpetuation of inflammation probably requires additional stimuli.
Alanine Transaminase/blood, Animals, Antibodies, Antineutrophil Cytoplasmic/analysis, C-Reactive Protein/analysis, Cholangitis, Sclerosing/pathology, Chronic Disease, Disease Models, Animal, Disease Progression, Female, Humans, Liver/pathology, Rats, Rats, Inbred Lew, Trinitrobenzenesulfonic Acid/toxicity
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