Endotoxin clearance and its relation to hepatic and renal disturbances in rats with liver cirrhosis

Background/Aims: Little is known about endotoxin clearance and secretion of cytokines from macrophages in liver cirrhosis. The aims of this study were to investigate the relationship of endotoxin clearance and release of tumo r necrosis factor alpha by various macrophages to hepatic and renal disturb ances in liver cirrhosis. Methods: Male Sprague-Dawley rats were given 0.04 % thioacetamide orally for 6 or 12 months. The organ distribution of infuse d [H-3]-endotoxin (10 mug/kg b.w.) was analyzed at 30 min or at 24 h. Uptak e of [H-3]-endotoxin and secretion of tumor necrosis factor alpha by Kupffe r cells, splenic macrophages and peripheral blood monocytes (1 X 10(4) cell s/ml) from cirrhotic and control rats were determined. Results: In cirrhoti c rats, more endotoxin was left in the body and more endotoxin accumulated in the spleen and kidney, and thus was related to elevation of serum total bilirubin, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine and tumor necrosis factor alpha. Endotoxin uptake and tumor necrosis factor alpha release by the Kupffer cells were decreased an d those by the splenic macrophages and peripheral blood monocytes were incr eased in cirrhotic rats. Conclusions: In liver cirrhosis, impaired clearanc e of endotoxin together with increased secretion of tumor necrosis factor a lpha by extrahepatic macrophages may play an important role in the progress ion of hepatic and renal disturbances.