Effect of Kupffer cell phagocytosis blockade on endotoxin sensitivity, endotoxin induced-cytokine production in obstructive jaundice

Bacterial endotoxin is primarly responsible for the increased number of com plications in patients with jaundice. In endotoxin/septic shock the release of highly reactive materials from the Kupffer cells may contribute to the development of multiple organ failure"." The effect of GdCl3-induced blocka de of Kupffer cell phagocytosis on endotoxin sensitivity, endotoxin induced cytokine production and hepatotoxicity was studied in in vivo experiments using rats with obstructive jaundice. Obstructive jaundice greatly sensitiz ed the animals to bacterial lipopolysacharide (LPS) and LPS induced tumor n ecrosis factor-alpha (TNF-alpha) production. GdCl3 significantly increased the resistance of animals with jaundice againts bacterial endotoxin, reduce d LPS induced TNF-alpha production. GdCl3 significantly reduced the serum l evel of GOT (ASAT) and GPT (ALAT) compared to controls 4 hours after the en dotoxin challenge. This protective effect was not observed on serum GGT lev el. The results underline the importance of Kupffer cell function and the a ctivation of inflammatory cytokines in the increased morbidity in obstructi ve jaundice.