Obstructive jaundice alters Kupffer cell function independent of bacterial translocation.
BACKGROUND
There is a high incidence of perioperative morbidity and mortality in patients with obstructive jaundice. The absence of bile in the gastrointestinal tract promotes bacterial overgrowth and the increased translocation of bacteria and endotoxin to the liver which has been postulated to inhibit Kupffer cell function in these patients. But, biliary tract obstruction can directly damage liver cells and thus alter their function. Thus, we hypothesized that obstructive jaundice alone alters Kupffer cell function independent of the effects of bacterial translocation. This study was designed to evaluate the contribution of bacterial translocation to the altered Kupffer cell function observed in patients with obstructive jaundice.


METHODS
Sprague-Dawley rats were randomized to three groups of six animals each. Group 1 underwent common bile duct ligation with intestinal bile salt replacement (sodium taurocholate 100 mg/kg/day) via gastrostomy and an implantable osmotic pump (CBDL + bile salts), Group 2 underwent common bile duct ligation with normal saline replacement (CBDL + saline), and Group 3 underwent a sham operation (sham control). After 7 days, tissue and blood were collected for bacterial translocation and biochemical analyses. Examination of cultured Kupffer cell function included measuring the phagocytosis of heat-killed Candida albicans and endotoxin (LPS)-induced TNFalpha and nitric oxide production.


RESULTS
While bacterial translocation and cecal bacterial counts were significantly increased in the CBDL + saline group, these parameters were both reduced to control levels following intestinal bile salt replacement (CBDL + bile salts). Altered Kupffer cell function, as measured by the increased phagocytosis of C. albicans and LPS-induced NO production, and decreased LPS-induced TNFalpha production were observed in all animals with obstructive jaundice regardless of bile salt replacement.


CONCLUSIONS
Kupffer cell function appears to be differentially affected by obstructive jaundice and these altered functions can occur independent of bacterial translocation.
Sheen-Chen
S M
SM
Department of Surgery, San Francisco General Hospital, University of California at San Francisco, San Francisco, California, 94110, USA.
Chau
P
P
Harris
H W
HW
D000818:Animals; D001647:Bile Acids and Salts / Q000008:administration & dosage; D002779:Cholestasis / Q000382:microbiology* / Q000503:physiopathology*; D015169:Colony Count, Microbial; D003135:Common Bile Duct / Q000601:surgery; D004064:Digestive System / Q000382:microbiology; D006801:Humans; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology*; D008026:Ligation; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000382:microbiology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D001647:Bile Acids and Salts; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide