Biliary interleukin 6 levels as indicators of hepatic allograft rejection in rats

Interleukin 6 has recently been noted to be present during the rejection response to grafted organs. In this study, we investigated biliary and serum interleukin 6 levels following liver transplantation in rats. IL-6 levels in bile and serum of naive rats were below 0.6 U/ml and 0.5 +/- 0.2 U/ml (mean +/- SD), respectively. Both biliary and serum IL-6 levels showed high values (greater than 10.0 U/ml and greater than 1.6 U/ml, respectively) on the day after transplantation, which seemed to reflect the inflammatory status caused by the surgical stress. Later samplings showed that the kinetics of serum IL-6 differed among the animals without any definite feature related to graft rejection. In contrast, biliary IL-6 levels correlated well with the severity of the rejection response as determined histologically. Biliary IL-6 levels started to rise at the onset of the rejection response (6.6 +/- 0.6 U/ml), increased further with its progression (19.3 +/- 7.8 U/ml), and then finally fell in the terminal stage (less than 2.0 U/ml). Elevation of biliary IL-6 was observed at an early stage when abnormalities could be detected histologically but not in liver function tests and bile flow. Therefore, biliary IL-6 levels may be of value for the early diagnosis of rejection following liver transplantation.