Phenotypic analysis of inflammatory infiltrate in rats with dimethylnitrosamine-induced cirrhosis

The present study is concerned with the immunohistochemical characterization in situ of the mononuclear infiltrate accompanying the formation of septa and the development of cirrhosis in the liver of rats treated with dimethylnitrosamine (DMN), i.p. (10 microliters/kg, 3 days a week for 3 weeks). Monoclonal antibodies against macrophages, pan T cells, T cell subsets and B cells have been applied on cryostat sections of animals given DMN for 7, 14 and 21 days. The maximum increase of macrophages and lymphocytes was observed at days 7 and 14 respectively. At all times T lymphocytes appeared as the major component of the inflammatory infiltrate with a largely predominant population of cytotoxic/suppressor T cells. At day 21, with evidence of nodulation of parenchyma, macrophages levelled off while T cells remained numerous without changes in the inducer-helper T cells/cytotoxic-suppressor T cells ratio which remained always less than 1. B cells were always few. These findings illustrate the early influx of lymphocytes in DMN-induced liver injury and help to define the lymphocyte subsets associated with inflammation and fibrosis in a reproducible animal model.