An experimental animal model of primary biliary cirrhosis induced by lipopolysaccharide and pyruvate dehydrogenase

Previously, we found that the antibody titer belonging to the IgM class produced against the bacterial antigen (Lipid A) was elevated in sera from patients with primary biliary cirrhosis (PBC). On the other hand, the targets of the mitochondrial autoantibodies have been identified as being components of the pyruvate dehydrogenase complex (PDH). We tried to produce an experimental animal model for the investigation of the association between hepatic bile duct alteration and bacterial infection. Female C57/BL mice, aged 4 weeks, were used. An emulsion consisting of lipopolysaccharide (LPS) derived from Salmonella minnesota Re595, PDH, and Freund's adjuvant was prepared. This emulsion was subcutaneously injected on the back of the mice. The mice were divided into a control group (n = 5), a group given LPS (n = 5) alone, those given PDH alone (n = 5), and those given a combination of LPS and PDH (n = 5). The antigens were administered once a week every week with a maximum duration of administration of 24 weeks. The serum levels of IgM after 24 weeks in the LPS and LPS + PDH groups were 2.5 times higher than those in the control and PDH groups. The light microscopic findings of liver tissue revealed that infiltration of lymphocytes and plasma cells in the portal area, proliferation of the bile duct, and degeneration of the biliary epithelial cells were more prominent in the PDH and LPS + PDH groups than in the other groups. These results indicate that our animal model may be useful in investing the pathogenesis of PBC.