Characterization of the Kupffer cell response to exogenous endotoxin in a rodent model of obstructive jaundice

Background: Sepsis and endotoxaemia occur frequently in biliary obstruction . Impaired Kupffer cell endocytosis is implicated in these events. Tumour n ecrosis factor and interleukin 6, secreted by Kupffer cells, are important mediators of sepsis. Kupffer cell clearance of endotoxin and secretion of c ytokines in experimental obstructive jaundice were investigated. Methods: Wistar rats were randomized to bile duct ligation, sham operation or control. Groups (n = 8) were studied 1 and 3 weeks after operation. Kupf fer cell function was assessed using in situ hepatic perfusion. Results: Clearance of endotoxin was significantly depressed 1 week (median (interquartile range) 20.3 (10.5-27.1) per cent) and 3 weeks (22.1 (20.2-23 .2) per cent) after bile duct ligation compared with that in respective sha m animals (35.5 (29.9-41.6) and 40.9 (37.7-47.0) per cent) and controls (39 .5 (37.3-46.8) per cent). Secretion of tumour necrosis factor was significa ntly greater 1 week (1113.7 (706.5-1436.8) pg/ml) and 3 weeks (1118.2 (775. 7-1484.1) pg/ml) following bile duct ligation compared with that in respect ive sham animals (114.3 (0-178.5) and 107.6 (63.7-166.4) pg/ml) and control s (0 (0-20.7) pg/ml). Interleukin 6 was not secreted by sham or control ani mals but was present in the perfusate from jaundiced animals at 1 and 3 wee ks (52.5 (9.9-89.5) and 66.2 (60.2-193.1) pg/ml). Conclusion: These data demonstrate simultaneous impairment of Kupffer cell clearance of endotoxin and increased secretion of proinflammatory cytokines in experimental obstructive jaundice. These diverse responses may contribu te to the development of sepsis-related complications in biliary obstructio n.