肝硬変における血中エンドトキシン不活性化機構に関する研究 : アルブミンの意義

Abstract

Endotoxin binding and inactivating abilities of albumin were evaluated in patients with liver cirrhosis. Endotoxin binding capacity of albumin was significantly lower in Child C cirrhotics than that in Child A cirrhotics. There was a significant negative correlation between endotoxin binding capacity of albumin and Child-Pugh score. Plasma endotoxin inactivating rate in Child C cirrhotics was significantly lower than that in Child A cirrhotics, although plasma endotoxin inactivating rate in cirrhotics was generally greater than that in healthy subjects. Plasma endotoxin inactivating rate was positively related to endotoxin binding capacity of albumin. Endotoxin binding capacity of albumin was positively related to serum albumin and high density lipoprotein (HDL)-cholesterol. The addition of human albumin to cirrhotic plasma resulted in a significant increase in endotoxin binding capacity of HDL. Plasma interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were negatively related to serum albumin. Plasma samples with high amounts of IL-1β, IL-6 and TNF-α showed marked decrease in endotoxin binding capacity of albumin. Albumin at concetrations of 1.5 or 3.0 g/dl was proved to inactivate 80 to 90 % of 250 pg/ml endotoxin in the chromogenic assay system. Albumin (10-1000 mg /dl) inhibited endotoxin uptake and TNF production by Kupffer cells in a rat experimental model. These results suggest that albumin is an important endotoxin binding protein which inactivates endotoxin and suppresses cytokine secretion from the Kupffer cells in liver cirrhosis. Thus, administration of albumin is considered to be beneficial to endotoxin inactivation in patients with advanced liver cirrhosis.