Dimethylnitrosamine-induced cirrhosis. Evidence for an immunological mechanism.

The present study is concerned with the early events associated with the development of cirrhosis induced by dimethylnitrosamine (DMN). The antigenic expression of MHC class II components (Ia) and of some intermediate filament proteins (vimentin and desmin) have been studied by immunohistochemistry and the findings correlated with ultrastructural data. Micronodular cirrhosis developed after 3 weeks of treatment with DMN but enhanced expression of Ia antigen on macrophages and on infiltrating lymphocytes was observed after 1 week, before the formation of septa, suggesting that immune-mediated mechanisms are involved in the response to DMN-induced liver injury. The expression of vimentin and of desmin also increased at an early stage and at 3 weeks the septa were outlined by cellular elements showing positivity for both intermediate filament proteins. In keeping with these observations, ultrastructural data showed active division of macrophages in situ, infiltration of the parenchyma by T and B lymphocytes, activation of lipocytes (Ito cells) showing evidence of mitosis, and the presence of transitional elements between lipocytes, myofibroblasts and fibroblasts. This experimental model may be helpful in understanding the relationship between immune-mediated response to liver injury and development of hepatic fibrosis.