Obstructive jaundice in rats results in exaggerated hepatic production of tumor necrosis factor-alpha and systemic and tissue tumor necrosis factor-alpha levels after endotoxin.
BACKGROUND
Obstructive jaundice (OJ) predisposes patients to postoperative sepsis. We determined whether OJ led to an increased endotoxin stimulated tumor necrosis factor-alpha (TNF-alpha) production by macrophage-rich organs and whether a lack of intraluminal gut bile contributed to this increased sensitivity.


METHODS
Rats underwent laparotomy and common bile duct ligation and division (CBDL) or sham operation after they were given low-dose endotoxin or saline solution (NS). TNF-alpha levels in plasma, perfusate from the isolated perfused rat liver, and tissue from lung, spleen, and liver were measured 90 minutes later. An additional group underwent creation of a choledochal-vesical fistula and endotoxin administration.


RESULTS
The plasma TNF-alpha, liver perfusate TNF-alpha, and the tissue TNF-alpha levels in liver, lung, and spleen were significantly elevated in the CBDL + endotoxin (CBDL + ETX) group compared with the SHAM + ETX and CBDL + NS groups (p < 0.05). The choledochal-vesical fistula group after endotoxin had plasma TNF-alpha levels only 27% that of the CBDL + ETX group (p < 0.05).


CONCLUSIONS
OJ sensitizes macrophage-rich organs to produce larger amounts of TNF-alpha in response to endotoxin. This sensitization is not solely due to decreased intraluminal gut bile.
O'Neil
S
S
Department of Surgery, Loyola University Medical Center, Maywood, IL 60153, USA.
Hunt
J
J
Filkins
J
J
Gamelli
R
R
D000818:Animals; D001663:Bilirubin / Q000097:blood; D002779:Cholestasis / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D003135:Common Bile Duct / Q000502:physiology; D003137:Common Bile Duct Diseases; D004731:Endotoxins / Q000494:pharmacology*; D005402:Fistula; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology*; D008168:Lung / Q000276:immunology / Q000503:physiopathology; D008297:Male; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012477:Salmonella enteritidis; D013154:Spleen / Q000276:immunology / Q000503:physiopathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D001745:Urinary Bladder Diseases
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D001663:Bilirubin