The Role of Immunosuppression in Ex Vivo Lung Perfusion: A Systematic Review.

BACKGROUND: Ex vivo lung perfusion (EVLP) allows for prolonged preservation of donor lungs; however, inflammation during EVLP has been a persistent concern, despite previous attempts to minimize inflammation. Herein, we perform a systematic review investigating the efficacy of various approaches to reducing immune response and inflammation during EVLP. METHODS: A literature search of PubMed and Embase was conducted, including all articles describing all human or animal investigations of immunosuppression or proinflammatory cytokine inhibition in the settings of EVLP. RESULTS: A total of 643 articles were identified, and 19 met the inclusion criteria. Among these, models utilized were 10 porcine, 5 rat, 1 murine, 1 rabbit, and 2 human studies, representing a combined total of 411 subjects. Complement inhibition consistently improved oxygenation. IL-10 gene therapy reduced IL-1β, IL-6, and IL-8 while increasing IL-10, translating into lower pulmonary vascular resistance, improved oxygenation, and reduced edema. Cyclosporine reduced IL-1β and IL-6 and improved oxygenation at low doses but was detrimental at higher doses. Antiinflammatory modulation broadly decreased IL-6, IL-1β, IL-10, INF-γ, IL-18, and TNFα, with improvements in compliance and reduced airway pressures. Finally, adenosine A2A receptor agonists consistently reduced TNFα and INF-γ, lowered pulmonary artery pressure, increased compliance, and reduced edema. CONCLUSIONS: This systematic review identified numerous studies with various approaches that aim to reduce inflammation during EVLP. The majority of the methods investigated improved select measures of lung function, with no single approach resulting in widespread improvements. A combination of immunosuppressive or antiinflammatory interventions may be required to adequately address the inflammatory response during EVLP.