Effect of hepatic injury on adjuvant arthritis.

Hench (1933) described the ameliorating effect of hepatic disease on rheumatoid arthritis. Although jaundice was thought to be the determining factor in these remissions, it was not possible to reproduce the phenomenon by administration of bilirubin and bile salts (Hench, 1940), and a satisfactory explanation of its mechanism has never been offered (Hill and Holley, 1966). This was investigated in the present study using the rat adjuvant arthritis (AA) model. With the hepatotoxin dimethylnitrosamine (DMN), it is possible to produce a necrotizing hepatitis, which resolves rapidly, resulting in a virtually normal histological appearance in about 2 weeks (Barnes and Magee, 1954). SinceDMN is converted by the action of liver enzymes to an alkylating intermediate which, in turn, is rapidly inactivated, it functions as a selective hepatotoxin (Magee and Swann, 1969). Thus a brief but severe episode of liver injury may be superimposed on AA at various points during its induction and course.