Role of the spleen in endotoxin-induced hepatic injury in chronic alcohol-fed rats.

The present experiments were designed to study the role of the spleen in endotoxin-induced hepatic injury in chronic alcohol-fed rats. Administration of 2 mg/kg body weight of endotoxin caused severe hepatic injury in chronic alcohol-fed rats as compared with controls. This injury was significantly less in those whose spleens had been resected 1 week prior to endotoxin administration. There were no differences in plasma endotoxin levels 16 h after intravenous injection of endotoxin between sham-operated control rats, and chronic alcohol-fed rats with and without splenectomy. The plasma tumor necrosis factor (TNF) level 1 h after intravenous injection of endotoxin was significantly higher in chronic alcohol-fed rats than in controls. However, TNF levels were significantly lower in those with splenectomy. Neutrophil infiltration was seen in the liver sinusoid of sham-operated chronic alcohol-fed rats as early as 1 h after injection of endotoxin, and was observed even 15 h later. These results suggest that endotoxin-induced liver injury is closely related to factors derived from the spleen and induced by plasma endotoxin, especially when Kupffer cell function is reduced by chronic alcohol feeding. In addition, TNF and neutrophils may play an important role in this type of liver injury.