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The role of interleukin-1β as a predictive biomarker and potential therapeutic target during clinical ex vivo lung perfusion

Lookup NU author(s): Anders Andreasson, Dr Lee Borthwick, Dr Colin Gillespie, Kasim Jiwa, Jonathan Scott, Professor Simi Ali, Professor John Dark, Professor Andrew Fisher

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

© 2017 The Authors. Background: Extended criteria donor lungs deemed unsuitable for immediate transplantation can be reconditioned using ex vivo lung perfusion (EVLP). Objective identification of which donor lungs can be successfully reconditioned and will function well post-operatively has not been established. This study assessed the predictive value of markers of inflammation and tissue injury in donor lungs undergoing EVLP as part of the DEVELOP-UK study. Methods: Longitudinal samples of perfusate, bronchoalveolar lavage, and tissue from 42 human donor lungs undergoing clinical EVLP assessments were analyzed for markers of inflammation and tissue injury. Levels were compared according to EVLP success and post-transplant outcomes. Neutrophil adhesion to human pulmonary microvascular endothelial cells (HPMECs) conditioned with perfusates from EVLP assessments was investigated on a microfluidic platform. Results: The most effective markers to differentiate between in-hospital survival and non-survival post-transplant were perfusate interleukin (IL)-1β (area under the curve = 1.00, p = 0.002) and tumor necrosis factor-α (area under the curve = 0.95, p = 0.006) after 30 minutes of EVLP. IL-1β levels in perfusate correlated with upregulation of intracellular adhesion molecule-1 in donor lung vasculature (R 2 = 0.68, p < 0.001) and to a lesser degree upregulation of intracellular adhesion molecule-1 (R 2 = 0.30, p = 0.001) and E-selectin (R 2 = 0.29, p = 0.001) in conditioned HPMECs and neutrophil adhesion to conditioned HPMECs (R 2 = 0.33, p < 0.001). Neutralization of IL-1β in perfusate effectively inhibited neutrophil adhesion to conditioned HPMECs (91% reduction, p = 0.002). Conclusions: Donor lungs develop a detectable and discriminatory pro-inflammatory signature in perfusate during EVLP. Blocking the IL-1β pathway during EVLP may reduce endothelial activation and subsequent neutrophil adhesion on reperfusion; this requires further investigation in vivo.


Publication metadata

Author(s): Andreasson ASI, Borthwick LA, Gillespie C, Jiwa K, Scott J, Henderson P, Mayes J, Romano R, Roman M, Ali S, Fildes JE, Marczin N, Dark JH, Fisher AJ, on behalf of the DEVELOP-UK Investigators

Publication type: Article

Publication status: Published

Journal: Journal of Heart and Lung Transplantation

Year: 2017

Volume: 36

Issue: 9

Pages: 985-995

Print publication date: 01/09/2017

Online publication date: 12/05/2017

Acceptance date: 02/04/2016

ISSN (print): 1053-2498

ISSN (electronic): 1557-3117

Publisher: Elsevier

URL: https://doi.org/10.1016/j.healun.2017.05.012

DOI: 10.1016/j.healun.2017.05.012


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