Enhanced endotoxin clearance in reversed Eck fistula rats during a tolerant stage

The effects of tolerance to Escherichia coli endotoxin on the clearance activity of the hepatic reticuloendothelial system was examined using the experimental animal model of the reversed Eck fistula (REF). Compared with clearance rate of 51Cr-labeled endotoxin in the normal REF-rat, in the tolerant reversed Eck fistula animals, there was three fold increase in the clearance of endotoxin in the liver. The enhanced endotoxin uptake of the hepatic reticuloendothelial system was observed when the medium containing serum from tolerant animals was infused into the non-tolerant liver with a Harvard pump before the clearance studies, using 51Cr-labeled endotoxin administered via the femoral vein. Heat treatment of tolerant serum at 56 degrees C for 45 min destroyed the enhancing effect. These results suggest that during endotoxin tolerance, humoral factors, particularly complement, play an important role in the uptake of endotoxin from portal vein blood. A direct stimulation of the hepatic reticuloendothelial system may also occur.