Early development of primary biliary cirrhosis in female C57BL/6 mice because of poly I:C administration

Abstract Background: Primary biliary cirrhosis (PBC) is one of the organ‐specific autoimmune diseases characterized by destruction of the biliary epithelial cells, cholestasis, liver cirrhosis, and liver failure. With the postulation that induction of the autoimmune process might induce PBC‐like cholangitis, here we used polyinosinic polycytidylic acid (poly I:C), an inducer of type‐1 interferon (IFN), to generate an autoimmune cholangitis animal model. Methods: Female C57BL/6 mice were injected with 5 mg/kg of poly I:C twice a week for 28 consecutive weeks. Liver specimens were collected to evaluate the degree of cell infiltration. Autoantibodies, including antimitochondrial antibody (AMA), were assayed by immunofluorescence, enzyme‐linked immunosorbent assay (ELISA) and immunoblotting. IFN‐α was estimated in the sera by an ELISA method. Poly I:C injection induced IFN‐α. Results: Mononuclear cells were detected at the portal areas 8 weeks after the start of poly I:C injection, which progressed up to 16 weeks. Autoantibodies, including AMA, were detected in the sera from all poly I:C‐injected mice. Conclusions: In conclusion, we show an early development of a PBC‐like cholangitis in a genetically susceptible mouse strain because of poly I:C administration. This model would be helpful to study PBC immunopathogenesis and to evaluate the effectiveness of newly developed therapeutic regimens for PBC.