Animal models for primary sclerosing cholangitis

doi:10.1053/bega.2001.0207

Best Practice & Research Clinical Gastroenterology

Volume 15, Issue 4, August 2001, Pages 591-610

https://doi.org/10.1053/bega.2001.0207 Get rights and content

Abstract

Since the aetiopathogenesis of primary sclerosing cholangitis (PSC) in humans remains undefined, investigators have studied a variety of animal models to gain insights into immunopathogenetic mechanisms associated with obliterative fibrous cholangitis of intra- and extra-hepatic bile ducts. To date, no animal model has been developed that exhibits all of the attributes of PSC. Rodent models instigated by bacterial cell components or colitis are promising because they may help to explain the strong association between PSC and inflammatory bowel disease (IBD). Other models of direct injury to biliary epithelia, peribiliary vascular endothelia or portal venous endothelia indicate that inflammation, chemokines and cytokines can produce diffuse sclerosis of bile ducts. Models of toxic, infectious or intra-luminal injury of the biliary tract also exhibit focal biliary sclerosis mediated by inflammation and cytokines. The histopathology of several models suggests a sequence of events beginning with secretion of proinflammatory cytokines by activated hepatic macrophages followed by peribiliary infiltration with CD4 and CD8 T cells with a T helper 1 phenotype. These results strongly suggest co-ordinated, pathogenetic roles for both the innate and adaptive immune responses. However, the stimuli that initiate and perpetuate peribiliary fibrosis remain unknown. Interestingly, several models are also associated with the development of anti-neutrophil cytoplasmic antibodies that react in a perinuclear and cytoplasmic pattern similar to that observed in patients with ulcerative colitis and/or PSC. Finally, models of extra-hepatic biliary obstruction continue to provide important information about the pathogenesis of portal fibrosis and secondary biliary cirrhosis that occurs in PSC and other diseases with obstruction of bile flow. Future studies in either existing or new animal models should advance our understanding of the pathogenesis of PSC, the major prerequisite for the development of effective therapies.

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Regular ArticleAnimal models for primary sclerosing cholangitis

Abstract

Human Pathology

Gastroenterology

Journal of Hepatology

Gastroenterology

Journal of Hepatology

Academic Radiology

Baillière's Clinical Rheumatology

Gastroenterology

Gastroenterology

Gastroenterology

Mayo Clinic Proceedings

Gastroenterology

American Journal of Medicine

Journal of Hepatology

Journal of Hepatology

Journal of Hepatology

Academic Radiology

Journal of Hepatology

Primary sclerosing cholangitis

Disappearing intrahepatic bile ducts: the syndromes and their mechanisms

Seminars in Liver Disease

Immunogenetics and epidemiology of primary sclerosing cholangitis

HLA class II haplotypes in primary sclerosing cholangitis patients from five European populations

Tissue Antigens

Hyperplasia of bile ducts induced by ANIT: experimental biliary cirrhosis free from biliary obstruction

Journal of Pathology and Bacteriology

Segregation of pANCA antigenic recognition by DNase treatment of neutrophils: ulcerative colitis, type 1 autoimmune hepatitis, and primary sclerosing cholangitis

Journal of Clinical Immunology

Phage display cloning and characterization of an immunogenetic marker (perinuclear anti-neutrophil cytoplasmic antibody) in ulcerative colitis

Journal of Immunology

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Immunological Reviews

pANCA represents a cross-reactivity to enteric bacterial antigens

Journal of Clinical Immunology

Identification of Helicobacter pylori and other Helicobacter species by PCR, hybridization, and partial DNA sequencing in human liver samples from patients with primary sclerosing cholangitis or primary biliary cirrhosis

Journal of Clinical Microbiology

Comparison of peptidoglycan-polysaccharide and lipopolysaccharide stimulation of Kupffer cells to produce tumor necrosis factor and interleukin-1

Hepatology

Bacterial cell wall polymers (peptidoglycan-polysaccharide) cause reactivation of arthritis

Infection and Immunity

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Journal of Clinical Investigation

Biliary tract disease in rats with experimental small bowel bacterial overgrowth

Hepatology

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Infection and Immunity

Hepatobiliary injury associated with experimental small-bowel bacterial overgrowth in rats

Immunologic Research

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Gastroenterology

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Journal of Experimental Medicine

Extraintestinal manifestations of granulomatous enterocolitis induced in rabbits by long-term submucosal administration of muramyl dipeptide emulsified with Freund's incomplete adjuvant

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Regular Article
Animal models for primary sclerosing cholangitis