Downregulation of cytokine-induced neutrophil chemoattractant and prolongation of rat liver allograft survival by interleukin-10.

We investigated whether the administration of recombinant human interleukin-10 (rhIL-10) regulates the production of cytokine-induced neutrophil chemoattractant (CINC) and improves graft survival in rat orthotopic liver transplantation (OLTx). Allograft recipients received injections of rhIL-10 at doses of 2, 10, 20, or 50 micrograms/kg/day. The allograft recipients that received rhIL-10 at 10 or 20 micrograms/kg/day showed a slight but significant prolongation of graft survival to 13.0 +/- 0.4 and 13.8 +/- 0.3 days, respectively, compared with 9.6 +/- 0.2 days in untreated 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 OLTx were reduced significantly compared with those in the no-treatment group. The mean peak neutrophil counts in the peripheral circulation (PC) of the groups given rhIL-10 at 10, 20, or 50 micrograms/kg/day from the samples obtained 12h after reperfusion were decreased significantly compared with the no-treatment group. Furthermore, the mean peak neutrophil counts in the PC of the groups given rhIL-10 at 10 or 20 micrograms/kg/day from the samples obtained between postoperative days (PODs) 7 and 10 were decreased significantly compared with the no-treatment group. The magnitude of liver damage and leukocyte infiltration in the rhIL-10-treated allografts on PODs 1 and 7 was reduced compared with that of untreated allografts. Our data indicate that the administration of rhIL-10 downregulates CINC production during the period of reperfusion injury and acute cellular rejection after OLTx, and prolongs liver allograft survival, suggesting that IL-10 therapy is potentially beneficial in OLTx.