[Consequences of Kupffer cell blockade on endotoxin-induced inflammatory and hepatic microcirculatory reactions during experimental biliary obstruction].
OBJECTIVE
In the clinical practice, biliary obstruction often leads to septic complications causing systemic and hepatic inflammatory reactions, which increases mortality and morbidity. Hepatic Kupffer cells (KC) play a pivotal role in this process. Herein we examined the consequences of bile duct ligation during endotoxaemia and the effects of KCs.


METHODS
In the first part of our experiment, the survival rate of male Wistar rats in 48-hr endotoxaemia with or without bile duct ligation was assessed. Time-dependent changes in pro-inflammatory TNF-alpha and IL-6 levels were also monitored. In the second series, hepatic capillary perfusion, neutrophil-endothelial interactions and KC activity were assessed using fluorescence intravital videomicroscopy. KC blockade was induced by gadolinium chloride (GdCl3) pretreatment.


RESULTS
Serum TNF-alpha and IL-6 levels were significantly increased in early endotoxaemia. Survival rate was deteriorated, while TNF-alpha and IL-6 releases, KC activity and leukocyte activation were increased if obstructive jaundice was also induced. KC blockade improved survival and reduced TNF-alpha and IL-6 productions without ameliorating perfusion failure.


CONCLUSIONS
In the presence of biliary obstruction, inflammatory and microcirculatory consequences of endotoxaemia are enhanced. The alleviating effect of KC blockade may underline the pathophysiological role of KCs in these conditions.
Abrahám
Szabolcs
S
Szegedi Tudományegyetem, Altalános Orvostudományi Kar, Sebészeti Klinika, 6720 Szeged, Pécsi u. 6.
Szabó
Andrea
A
Paszt
Attila
A
Duda
Erno
E
Lázár
György
G
Lázár
György
G
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001659:Biliary Tract / Q000473:pathology*; D015415:Biomarkers / Q000097:blood; D003251:Constriction, Pathologic / Q000503:physiopathology; D019446:Endotoxemia / Q000150:complications; D004731:Endotoxins; D005682:Gadolinium / Q000494:pharmacology*; D007249:Inflammation / Q000517:prevention & control; D015850:Interleukin-6 / Q000097:blood; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects; D008026:Ligation; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005682:Gadolinium; C038958:gadolinium chloride