Kupffer cell phagocytosis blockade decreases morbidity in endotoxemic rats with obstructive jaundice.
OBJECTIVE
The consequences of Kupffer cell phagocytosis blockade were studied in endotoxemic rats with obstructive jaundice.


METHODS
159 male Wistar rats.


METHODS
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.


CONCLUSIONS
Attenuation of Kupffer cell function decreases endotoxin-induced lethality and morbidity in obstructive jaundice.
Lázár
G
G
Department of Surgery, University of Szeged, Hungary. lg@surg.szote.u-szeged.hu
Paszt
A
A
Kaszaki
J
J
Duda
E
E
Szakács
J
J
Tiszlavicz
L
L
Boros
M
M
Balogh
A
A
Lázár
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002779:Cholestasis / Q000150:complications / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D019446:Endotoxemia / Q000150:complications / Q000473:pathology*; D005682:Gadolinium / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D007728:Kupffer Cells / Q000276:immunology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000255:Adenosine Triphosphate; D005682:Gadolinium; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C038958:gadolinium chloride