Prostaglandin E1 protects lung transplants from ischemia-reperfusion injury: A shift from pro- to anti-inflammatory cytokines

Introduction. Prostaglandin E-1 (PGE(1)) has been demonstrated to reduce is chemia-reperfusion (IR) injury following lung transplantation. However, the cytoprotective mechanisms remain largely unknown. The purpose of this stud y was to determine whether the mechanism through which PGE(1) improves IR i njury is related to the level of apoptosis or the release of inflammatory c ytokines. Methods. In a rat single-lung-transplant model, animals were randomly alloc ated into four groups of five animals each. Group 1 received normal saline (NS) in the preservation solution and during the 2-hr reperfusion period. G roup 2 received NS in the preservation solution and PGE(1) during the reper fusion period. Group 3 received PGE(1) in the preservation solution and NS during the reperfusion period. Group 4 received PGE(1) in the preservation solution and during the reperfusion period. Results. The two groups that received PGE, during the reperfusion period ha d a significantly higher partial pressure of oxygen (PaO2), lower wet-dry w eight ratio, and lower peak airway pressure at the end of the reperfusion p eriod than did the two groups that received NS. In the two groups that rece ived PGE(1) during the reperfusion period, we observed significantly higher levels of interleukin (IL)-10 in the transplanted lung tissue and plasma a nd significantly lower levels of tumor necrosis factor (TN-F)-alpha, interf eron (IFN)-gamma, and IL-12 in lung tissue. The levels of IL-4 and micropha ge inflammatory protein-2 (MIP-2) were not significantly different between groups. The number of apoptotic cells and the expression of Bcl-2 were not significantly different between groups. Conclusions. PGE(1) does not decrease the amount of apoptosis after reperfu sion and does not significantly upregulate Bcl-2. We have demonstrated that PGE(1) administered during the reperfusion period reduces IR injury and im proves lung function through a mechanism that is likely mediated by a shift between pro- and anti-inflammatory cytokine release.