Ali S

Barsby J

Bates L

Bigley V

Borthwick L

Charlton C

Dark J

Fisher AJ

Griffiths C

Macdonald J

Mavridou M

Morrison M

Pither T

Scott W

Wang L

Copyright \ua9 2023 The Author(s). Published by Wolters Kluwer Health, Inc. BACKGROUND: The association between interleukin-1β (IL-1β) concentrations during ex vivo lung perfusion (EVLP) with donor organ quality and post-lung transplant outcome has been demonstrated in several studies. The mechanism underlying IL-1β-mediated donor lung injury was investigated using a paired single-lung EVLP model. METHODS: Human lung pairs were dissected into individual lungs and perfused on identical separate EVLP circuits, with one lung from each pair receiving a bolus of IL-1β. Fluorescently labeled human neutrophils isolated from a healthy volunteer were infused into both circuits and quantified in perfusate at regular timepoints. Perfusates and tissues were subsequently analyzed, with perfusates also used in functional assays. RESULTS: Neutrophil numbers were significantly lower in perfusate samples collected from the IL-1β-stimulated lungs consistent with increased neutrophil adhesion ( P = 0.042). Stimulated lungs gained significantly more weight than controls ( P = 0.046), which correlated with soluble intercellular adhesion molecule-1 (R 2 = 0.71, P = 0.0043) and von-Willebrand factor (R 2 = 0.39, P = 0.040) in perfusate. RNA expression patterns for inflammatory genes were differentially regulated via IL-1β. Blockade of IL-1β significantly reduced neutrophil adhesion in vitro ( P = 0.025). CONCLUSION: These data illustrate the proinflammatory functions of IL-1β in the context of EVLP, suggesting this pathway may be susceptible to therapeutic modulation before transplantation

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Modeling the Effects of IL-1β-mediated Inflammation During Ex Vivo Lung Perfusion Using a Split Human Donor Model

Modeling the Effects of IL-1β-mediated Inflammation During Ex Vivo Lung Perfusion Using a Split Human Donor Model

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