SERUM INTERLEUKIN-6 LEVELS AS AN INDICATOR OF ACUTE REJECTION AFTER LIVER-TRANSPLANTATION IN CYNOMOLOGOUS MONKEYS

This study was designed to evaluate whether the sequential monitoring of serum interleukin-6 levels (SIL-6) could be helpful for diagnosing the occurrence of hepatic allograft rejection. An SIL-6 post-transplan t study was conducted on nine cynomolgus monkeys which had undergone o rthotopic hepatic allotransplantation, six of which were treated with FK-506 (a new immunosuppressant agent isolated from Streptomyces tsuku baensis) and three of which were not. All the nontreated animals showe d biochemical abnormalities from days 5-6, characterized by a marked e levation of serum alkaline phosphatase levels, and they eventually die d on days 8, 12, and 63 (group I). Acute cellular rejection was confir med by histological study of the hepatic grafts taken at autopsy or bi opsy. On the other hand, four of the treated animals (group IIa) survi ved more than 30 days. Biochemical examination of this group showed no abnormal signs apart from a slight elevation of alkaline phosphatase (<2000 IU/l). Histological examination carried out around 30 days afte r transplantation revealed a transient infiltration of polynuclear cel ls into Glisson's area, with the portal vein and bile duct remaining i ntact. The remaining two animals (group IIb) died of dehydration and a rterial thrombosis on days 5 and 7, respectively. A kinetic study of S IL-6 conducted during the first 2 weeks showed quite different pattern s among the three groups. All recipients in group I demonstrated two p eaks following grafting on days 1 and 3 or 4, the second peak of above 2.0 U/ml preceding biochemical abnormalities by 2 to 3 days. Converse ly, the recipients in group IIa showed a single peak of SIL-6 on day 1 , followed by a decrease to less than 2.0 U/ml. Group IIb characterist ically showed a high level of SIL-6 on day 1, after which the value re mained over 2.0 U/ml. In conclusion, the monitoring of SIL-6 proved us eful for detecting the acute rejection of hepatic allografts, the reci pients with rejected grafts displaying two peaks of SIL-6 after grafti ng. The first increment was observed on day 1, which might reflect the stress of the surgical procedure, while the second transient incremen t of SIL-6, observed on day 3 or 4, might suggest acute hepatic reject ion, preceding biochemical abnormalities by 2 to 3 days.