Expression of TNF-alpha and immunohistochemical distribution of hepatic macrophage surface markers in carbon tetrachloride-induced chronic liver injury in rats

In liver injury induced by carbon tetrachloride, secondary hepatic injury o ccurs from inflammatory processes originating from products released by act ivated Kupffer cells, which play a central role in hepatic inflammation. Th e purpose of our study was to demonstrate, in rats, the relationships betwe en a function of the hepatic macrophages, TNF-alpha production and the stat e of activation of these cells, characterized by their phenotype, in the di fferent phases of the process and development of fibrosis in a carbon tetra chloride-induced cirrhosis model. The immunohistochemical localization of p roinflammatory cytokine TNF-alpha and surface surface makers (ED1 and ED2) was studied in hepatitis and cirrhosis in response to 3 and 9 weeks ingesti on of carbon tetrachloride. After carbon tetrachloride ingestion, accompany ing the increased necrosis, immunohistochemical analysis of liver tissue se ctions demonstrated the significantly increased number of cells expressing ED1, ED2 and TNF-alpha, compared to normal. The number of cells expressing the surface phenotypic markers of liver macrophages increased and this chan ge was concomitantly associated with an increased cellular expression of TN F-alpha. Local macrophage proliferation and influx of newly recruited blood monocytes resulted in an increase of the macrophage population. The popula tional changes involved difference in functional activity and enhances TNF- alpha expression. This cytokine expressed in the carbon tetrachloride-induc ed inflammatory process is associated with the development of fibrosis and may contribute to disease severity.