Long-term evaluation of a rat model of chronic cholangitis resembling human primary sclerosing cholangitis

Scand J Immunol. 2003 Nov;58(5):533-40. doi: 10.1046/j.1365-3083.2003.01335.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Trinitrobenzenesulfonic Acid
  • C-Reactive Protein
  • Alanine Transaminase