Article ; Online: Modeling the Effects of IL-1β-mediated Inflammation During Ex Vivo Lung Perfusion Using a Split Human Donor Model.
2023 Volume 107, Issue 10, Page(s) 2179–2189
Abstract: 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 ... ...
| Abstract | 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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| MeSH term(s) | Humans ; Perfusion/adverse effects ; Interleukin-1beta/pharmacology ; Interleukin-1beta/metabolism ; Lung Transplantation/adverse effects ; Lung/metabolism ; Inflammation |
| Chemical Substances | Interleukin-1beta |
| Language | English |
| Publishing date | 2023-05-05 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 208424-7 |
| ISSN | 1534-6080 ; 0041-1337 |
| ISSN (online) | 1534-6080 |
| ISSN | 0041-1337 |
| DOI | 10.1097/TP.0000000000004613 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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