Cytokine response to portal endotoxaemia and neutrophil stimulation in obstructive jaundice

Eur J Gastroenterol Hepatol. 2012 Jan;24(1):25-32. doi: 10.1097/MEG.0b013e32834b0dd3.


Introduction: An exaggerated proinflammatory response to endotoxaemia can occur in obstructive jaundice. The aims of this study were to determine the hepatic proinflammatory and anti-inflammatory cytokine response to endotoxaemia in experimental biliary obstruction and to determine the source of interleukin-6 (IL-6) using immunohistochemistry.

Methodology: Male Wistar rats were randomized into three groups: bile duct ligation (BDL), sham operation, and control groups. They were weighed before surgery and after 1 week. On day 8, hepatic perfusion was performed with endotoxin (Escherichia coli 0111:B4). Serial samples of blood, effluent, and influent perfusate were analyzed for proinflammatory and anti-inflammatory cytokines. Ultrastructural assessment of sections of the liver was performed.

Results: BDL animals lost weight in the first week compared with the sham and the control animals that gained weight. Liver function tests were elevated in the BDL group. Effluent biochemistry did not reveal liver injury as a result of perfusion. Ultrastructurally, there was no evidence of liver injury, with only active Kupffer cells, preservation of liver architecture, and minimal liver injury being detected. Serum tumor necrosis factor-α was not detected in any group before perfusion; however, serum IL-6 was higher in the BDL group. Portal endotoxaemia resulted in an increase in tumor necrosis factor-α, IL-6, and IL-10 in the BDL group. Fluorescence immunohistochemistry demonstrated IL-6 in the sinusoidal spaces and the cytoplasm of Kupffer cells.

Conclusion: There is an exaggerated proinflammatory and anti-inflammatory cytokine response to portal endotoxaemia in animals with jaundice compared with the sham group.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / physiology
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Endotoxemia / complications
  • Endotoxemia / metabolism*
  • Endotoxemia / pathology
  • Inflammation Mediators / metabolism
  • Interleukins / metabolism
  • Jaundice, Obstructive / complications
  • Jaundice, Obstructive / metabolism*
  • Jaundice, Obstructive / pathology
  • Liver / metabolism
  • Liver / ultrastructure
  • Male
  • Microscopy, Electron
  • Neutrophil Activation
  • Neutrophils
  • Rats
  • Rats, Wistar
  • Respiratory Burst / physiology
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • Inflammation Mediators
  • Interleukins
  • Tumor Necrosis Factor-alpha