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 ischemia-reperfusion (IR) injury following lung transplantation. However, the cytoprotective mechanisms remain largely unknown. The purpose of this study was to determine whether the mechanism through which PGE(1) improves IR injury is related to the level of apoptosis or the release of inflammatory cytokines. Methods. In a rat single-lung-transplant model, animals were randomly allocated into four groups of five animals each. Group 1 received normal saline (NS) in the preservation solution and during the 2-hr reperfusion period. Group 2 received NS in the preservation solution and PGE(1) during the reperfusion 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 had a significantly higher partial pressure of oxygen (PaO2), lower wet-dry weight ratio, and lower peak airway pressure at the end of the reperfusion period than did the two groups that received NS. In the two groups that received PGE(1) during the reperfusion period, we observed significantly higher levels of interleukin (IL)-10 in the transplanted lung tissue and plasma and significantly lower levels of tumor necrosis factor (TN-F)-alpha, interferon (IFN)-gamma, and IL-12 in lung tissue. The levels of IL-4 and microphage 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 reperfusion and does not significantly upregulate Bcl-2. We have demonstrated that PGE(1) administered during the reperfusion period reduces IR injury and improves lung function through a mechanism that is likely mediated by a shift between pro- and anti-inflammatory cytokine release.