Increased concentrations of plasma IL-18 in patients with hepatic dysfunction after hepatectomy

Cytokine. 2000 Oct;12(10):1526-30. doi: 10.1006/cyto.2000.0740.


We investigated the dynamic aspects of circulatory IL-18 and other inflammatory cytokines in patients who underwent a hepatectomy. In patients with post-operative hepatic dysfunction, plasma concentrations of these cytokines increased, reflecting severe surgical trauma. IL-6, IL-10 and IFN-gamma increased in the early phase, while IL-18 increased in the later phase after 1 week. Interestingly, the increase in the plasma IL-18 concentration was correlated with that in serum bilirubin levels in hepatectomized patients. Hence, the decrease in the hepatic metabolism of IL-18 may cause the plasma accumulation of IL-18. This mechanism was confirmed using rat experiments. Intravenously administered human IL-18 was excreted into bile. Furthermore, the plasma clearance of human IL-18 was prolonged in bile duct-ligated rats. These results suggest that IL-18 is metabolized in the liver and excreted into bile, and an increase in plasma IL-18 in patients with hepatic dysfunction reflects the decreased metabolism in the liver.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Bile / metabolism
  • Bilirubin / blood
  • Fas Ligand Protein
  • Female
  • Hepatectomy / adverse effects*
  • Humans
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Interleukin-18 / blood*
  • Interleukin-18 / pharmacokinetics
  • Interleukin-6 / blood
  • Liver / metabolism*
  • Liver Diseases / blood*
  • Male
  • Membrane Glycoproteins / blood
  • Middle Aged
  • Rats
  • Rats, Wistar
  • Time Factors


  • FASLG protein, human
  • Fas Ligand Protein
  • Faslg protein, rat
  • Interleukin-18
  • Interleukin-6
  • Membrane Glycoproteins
  • Interleukin-10
  • Interferon-gamma
  • Bilirubin