EFFECTS OF PENTOXIFYLLINE PRETREATMENT ON KUPFFER CELLS IN RAT-LIVER TRANSPLANTATION

Previous research with pentoxifylline (PTX), a methylxanthine phosphod iesterase inhibitor, suggests that this drug may be capable of suppres sing the activation of Kupffer cells and thereby help decrease liver i njury after transplantation. To investigate this possibility, the curr ent study sought to determine whether the release of O-2(-) and tumor necrosis factor (TNF) from Kupffer cells in donor livers can be suppre ssed if the organs are exposed to PTX before preservation, In an in vi tro experiment, rat Livers were flushed with PTX (25 mg/kg body weight ) in University of Washington (UW) solution or UW solution alone (cont rol) and then and stored in UW solution for either 4 or 24 hours, Kupf fer cells then were purified and their degree of activation determined by measuring O-2(-) release and the production of TNF after lipopolys accharide stimulation. In an in vivo experiment, a group of rats under went orthotopic Liver transplantation with grafts prepared in the same manner as in the in vitro study, TNF and aspartate transaminase (AST) were measured in blood samples taken 3 hours and 24 hours after trans plantation. Compared with controls, the Kupffer cells from grafts pret reated with PTX produced significantly less O-2(-) and TNF, and the re cipients of PTX-pretreated grafts had lower levels of TNF and AST 3 ho urs after transplantation. The current data indicate that O-2(-) and T NF production in liver grafts is suppressed by PTX pretreatment, Throu gh its suppressive effect on Kupffer cells, PTX may help minimize pres ervation-reperfusion injury and improve graft survival.