Increased concentrations of plasma interleukin-18 in patients with hepatic failure 1 week after surgery.

We investigated the dynamic aspects of circulatory interleukin (IL)-18 in patients who underwent a hepatectomy. In patients with hepatic failure after surgery, plasma concentrations of IL-6 and IL-10 increased in the early phase; however, the plasma concentrations of 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 administrated human IL-18 was excreted in 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 in bile, and an increase in plasma IL-18 in patients with hepatic failure reflects the decreased metabolism in the liver.