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 necrosis factor and interleukin 6, secreted by Kupffer cells, are important mediators of sepsis. Kupffer cell clearance of endotoxin and secretion of cytokines 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. Kupffer 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 sham 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 significantly 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 respective sham animals (114.3 (0-178.5) and 107.6 (63.7-166.4) pg/ml) and controls (0 (0-20.7) pg/ml). Interleukin 6 was not secreted by sham or control animals but was present in the perfusate from jaundiced animals at 1 and 3 weeks (52.5 (9.9-89.5) and 66.2 (60.2-193.1) pg/ml).


CONCLUSIONS
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 contribute to the development of sepsis-related complications in biliary obstruction.
Kennedy
J A
JA
Department of Surgery, Queen's University of Belfast, Institute of Clinical Science, Grosvenor Road, Belfast BT12 6BJ, UK.
Clements
W D
WD
Kirk
S J
SJ
McCaigue
M D
MD
Campbell
G R
GR
Erwin
P J
PJ
Halliday
M I
MI
Rowlands
B J
BJ
D000818:Animals; D001652:Bile Ducts; D002779:Cholestasis / Q000378:metabolism*; D019446:Endotoxemia / Q000209:etiology; D004731:Endotoxins / Q000493:pharmacokinetics*; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000378:metabolism*; D008026:Ligation; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha