Increased concentrations of plasma IL-18 in patients with hepatic dysfunction after hepatectomy |
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Authors: | Shibata M Hirota M Nozawa F Okabe A Kurimoto M Ogawa M |
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Institution: | Department of Surgery II, Kumamoto University Medical School, 1-1-1 Honjo, Kumamoto-city, Kumamoto, 860-0811, Japan. |
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Abstract: | 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. |
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