DOWN-REGULATION OF CYTOKINE-INDUCED NEUTROPHIL CHEMOATTRACTANT AND PROLONGATION OF RAT-LIVER ALLOGRAFT SURVIVAL BY INTERLEUKIN-10

We investigated whether the administration of recombinant human interl eukin-10 (rhIL-10) regulates the production of cytokine-induced neutro phil chemoattractant (CINC) and improves graft survival in rat orthoto pic liver transplantation (OLTx). Allograft recipients received inject ions of rhIL-10 at doses of 2, 10, 20, or 50 mu g/kg/day. The allograf t recipients that received rhIL-10 at 10 or 20 mu g/kg/day showed a sl ight but significant prolongation of graft survival to 13.0 +/- 0.4 an d 13.8 +/- 0.3 days, respectively, compared with 9.6 +/- 0.2 days in u ntreated allografts. Conversely, the administration of high-dose rhIL- 10 shortened the allograft survival. In the rhIL-10 treatment groups, the mean serum and tissue levels of CINC at every time point after OLT x were reduced significantly compared with those in the no-treatment g roup. The mean peak neutrophil counts in the peripheral circulation (P C) of the groups given rhIL-10 at 10, 20, or 50 mu g/kg/day from the s amples obtained 12h after reperfusion were decreased significantly com pared with the no-treatment group. Furthermore, the mean peak neutroph il counts in the PC of the groups given rhIL-10 at 10 or 20 mu g/kg/da y from the samples obtained between postoperative days (PODs) 7 and 10 were decreased significantly compared with the no-treatment group. Th e magnitude of liver damage and leukocyte infiltration in the rhIL-10 treated allografts on PODs 1 and 7 was reduced compared with that of u ntreated allografts. Our data indicate that the administration of rhIL -10 downregulates CINC production during the period of reperfusion inj ury and acute cellular rejection after OLTx, and prolongs liver allogr aft survival, suggesting that IL-10 therapy is potentially beneficial in OLTx.