The Effect of Ex-Vivo Perfusion on the Inflammatory Cytokine Profile of the Donor Lung

Objectives: Ex-vivo lung perfusion (EVLP) may allow reconditioning of borderline donor lungs prior to transplantation. Although studies have demonstrated an improvement in physiological function, the effect of EVLP on lung inflammation is not yet established. We hypothesised that EVLP might contribute to reconditioning by decreasing proinflammatory cytokine levels in the donor lung. Methods: Five human donor lungs, deemed clinically unacceptable for transplantation were studied. Three underwent cellular and two acellular normothermic ex-vivo perfusion for 6 hours. Circulating perfusate was sampled hourly and a standardised bronchoalveolar lavage (BAL) was performed before and after 6 hours perfusion. Concentrations of IL-6, IL-8 and IL-10 were measured in BAL and perfusate using a sandwich ELISA technique. Results: The concentrations of IL-6, IL-8 and IL-10 in the perfusate increased significantly in a time dependent manner between 1 and 6 hours after perfusion was commenced (IL-6 13-fold, p=0.0062; IL-8 33-fold, p=0.0012; IL-10 2-fold, p=0.0068). Assessment of BAL showed no statistically significant changes in cytokine concentrations before or after EVLP, however BAL IL-8 concentrations showed a decreasing trend after perfusion (49.6ng/ml pre-perfusion and 34.3ng/ml post-perfusion p>0.05). IL-10 and IL-6 were not detectable in the pre-perfusion BAL samples but became detectable post-perfusion only in the acellularly perfused lungs. Conclusion: EVLP in clinically unacceptable donor lungs is associated with increases in pro-inflammatory and anti-inflammatory cytokines in the perfusate fluid over time. This effect may be attributable to a cytokine ‘wash-out’ from the lung into the perfusate fluid (Steen Solution, Vitrolife). The trends in BAL of increasing anti-inflammatory IL-10 and decreasing pro-inflammatory IL-8 cytokine concentrations, require further evaluation in more donors but may prove beneficial in improving donor lung function after transplantation.