INTERACTION OF KUPFFER CELLS TO SPLENIC MACROPHAGES AND HEPATOCYTES IN ENDOTOXIN CLEARANCE - EFFECT OF ALCOHOL

An additional administration of high dose ethanol to chronic alcohol-f ed rats led to a decrease in endotoxin clearance and an increase in en dotoxin accumulation in the spleen accompanied by an elevation of tumo ur necrosis factor (TNF) levels in the portal vein. Endotoxin uptake a nd TNF production by Kupffer cells (KC) and splenic macrophages in the chronic ethanol load rats were significantly greater than those in th e control rats. When these cells were precultured in the medium contai ning 10 to 100 mmol/L ethanol, the endotoxin uptake and TNF production of KC were decreased. However, this did not affect the endotoxin upta ke and TNF production of splenic macrophages. The hepatic production o f endotoxin binding protein was increased when KC were preincubated in the medium containing ethanol and the resultant culture supernatant w as added to the hepatocyte culture system. This endotoxin binding prot ein was proved to enhance the uptake of endotoxin and suppressed the p roduction of TNF in the KC. When KC and hepatocytes were isolated from chronically alcohol-fed rats, further addition of ethanol to the cult ure medium of KC did not affect the hepatic production of endotoxin bi nding protein. The increase in hepatic production of endotoxin binding protein may serve as a defence mechanism against endotoxicity. There is a possibility that an impairment of this defence mechanism has a pi votal role in the development of endotoxaemia and endotoxicity in chro nic alcoholics.