Long-term evaluation of a rat model of chronic cholangitis resembling human primary sclerosing cholangitis.
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.
Goetz
M
M
I. Medical Clinic, University of Mainz, Mainz, Germany. mgoetz@mail.uni-mainz.de
Lehr
H A
HA
Neurath
M F
MF
Galle
P R
PR
Orth
T
T
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D015209:Cholangitis, Sclerosing / Q000473:pathology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D019268:Antibodies, Antineutrophil Cytoplasmic; D014302:Trinitrobenzenesulfonic Acid; D002097:C-Reactive Protein; D000410:Alanine Transaminase