Kupffer cell phagocytosis blockade decreases morbidity in endotoxemic rats with obstructive jaundice

OBJECTIVE AND DESIGN: The consequences of Kupffer cell phagocytosis blockade were studied in endotoxemic rats with obstructive jaundice. MATERIAL OR SUBJECTS: 159 male Wistar rats. TREATMENT: Obstructive jaundice was induced by bile duct ligation (BDL). Gadolinium chloride (1 mg/100 g iv) was given 6 days after BDL to inhibit Kupffer cell activity and the animals were challenged with 1 microg/g endotoxin 24 h later. METHODS: Endotoxin sensitivity, tumor necrosis factor-alpha and interleukin-6 production were studied, liver and lung injury were assessed by neutrophil infiltration assay, tissue adenosine triphosphate, aspartate aminotransferase, alanine aminotransferase level determinations and histology, respectively. For statistics non-parametric methods were used. RESULTS: BDL sensitized the animals to endotoxin, increased endotoxin-induced tumor necrosis factor-alpha and interleukin-6 production and reduced ATP contents of the liver and the lung. Kupffer cell blockade significantly increased the resistance against endotoxin, diminished the inflammatory cytokine release and reduced endotoxin-induced tissue injury in BDL animals. CONCLUSION: Attenuation of Kupffer cell function decreases endotoxin-induced lethality and morbidity in obstructive jaundice.