Role of activated macrophages in augmentation of endotoxin hepatotoxicity.

In this study, to clarify the role of activated macrophages in the augmentation of endotoxin hepatoxicity, rats were pretreated with zymosan, an activator of macrophages, before the induction of endotoxin hepatotoxicity, and some were given pentoxifylline, an inhibitor of tumour necrosis factor production. The intravenous injection of zymosan induced many granulomas composed of macrophages in the lungs and the liver, while the intraperitoneal injection caused granulomas in the greater omentum. Endotoxin hepatotoxicity. as shown by focal and random hepatocellular coagulative necrosis and elevation of serum transaminase activities, was more intense in the rats pretreated with zymosan than in those which were not injected with zymosan. This augmented endotoxin hepatotoxicity was significantly inhibited by pentoxifylline treatment. These findings indicate that endotoxin hepatotoxicity may be augmented in the presence of activated macrophages which produce chemical mediators, particularly tumour necrosis factor.