Increased concentrations of plasma IL-18 in patients with hepatic dysfunction after hepatectomy.
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.
Shibata
M
M
Department of Surgery II, Kumamoto University Medical School, 1-1-1 Honjo, Kumamoto-city, Kumamoto, 860-0811, Japan.
Hirota
M
M
Nozawa
F
F
Okabe
A
A
Kurimoto
M
M
Ogawa
M
M
D000328:Adult; D000368:Aged; D000818:Animals; D001646:Bile / Q000378:metabolism; D001663:Bilirubin / Q000097:blood; D053222:Fas Ligand Protein; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D020382:Interleukin-18 / Q000097:blood* / Q000493:pharmacokinetics; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000097:blood*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D020382:Interleukin-18; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D016753:Interleukin-10; D007371:Interferon-gamma; D001663:Bilirubin