INTRODUCTION/AIMS: 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. MATERIAL AND 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.
|Translated title of the contribution||Consequences of Kupffer cell blockade on endotoxin-induced inflammatory and hepatic microcirculatory reactions during experimental biliary obstruction|
|Number of pages||6|
|Publication status||Published - Oct 2009|
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