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. 2023 Aug 14:36:10777.
doi: 10.3389/ti.2023.10777. eCollection 2023.

Cytokines Removal During Ex-Vivo Lung Perfusion: Initial Clinical Experience

Massimo Boffini  1 , Matteo Marro  1 , Erika Simonato  1 , Fabrizio Scalini  1 , Andrea Costamagna  2 , Vito Fanelli  2 , Cristina Barbero  1 , Paolo Solidoro  3 , Luca Brazzi  2 , Mauro Rinaldi  1
Affiliations

Cytokines Removal During Ex-Vivo Lung Perfusion: Initial Clinical Experience

Massimo Boffini et al. Transpl Int. .

Abstract

Ex Vivo Lung Perfusion (EVLP) can be potentially used to manipulate organs and to achieve a proper reconditioning process. During EVLP pro-inflammatory cytokines have been shown to accumulate in perfusate over time and their production is correlated with poor outcomes of the graft. Aim of the present study is to investigate the feasibility and safety of cytokine adsorption during EVLP. From July 2011 to March 2020, 54 EVLP procedures have been carried out, 21 grafts treated with an adsorption system and 33 without. Comparing the grafts perfused during EVLP with or without cytokine adsorption, the use of a filter significantly decreased the levels of IL10 and GCSFat the end of the procedure. Among the 38 transplanted patients, the adsorption group experienced a significant decreased IL6, IL10, MCP1 and GCSF concentrations and deltas compared to the no-adsorption group, with a lower in-hospital mortality (p = 0.03) and 1-year death rate (p = 0.01). This interventional study is the first human experience suggesting the safety and efficacy of a porous polymer beads adsorption device in reducing the level of inflammatory mediators during EVLP. Clinical impact of cytokines reduction during EVLP must be evaluated in further studies.

Keywords: cytokines; ex-vivo lung perfusion; inflammation; ischemia-reperfusion; lung transplant; primary graft dysfunction.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart of total ex-vivo lung perfusion procedures.
FIGURE 2
FIGURE 2
Flow chart of perfusate analysis during ex-vivo lung perfusion procedures.
FIGURE 3
FIGURE 3
Comparison of cytokines concentration in the perfusate at the beginning (T0) and at the end (Tf) of ex-vivo lung perfusion with and without CytoSorb® [base 10 log of IL6, panel (A); base 10 log of IL10, panel (B); base 10 log of MCP1, panel (C); base 10 log of GCSF, panel (D)]. Values are expressed as mean ± standard deviations. *p < 0.01 vs. T0; **p < 0.05 vs. T0; # p < 0.01 vs. no-Cytosorb group; ## p < 0.05 vs. no-Cytosorb group.
FIGURE 4
FIGURE 4
Comparison of cytokines concentration in the perfusate at the beginning (T0) and at the end (Tf) of ex-vivo lung perfusion with and without CytoSorb® in transplanted grafts [base 10 log of IL6, panel (A); base 10 log of IL10, panel (B); base 10 log of MCP1, panel (C); base 10 log of GCSF, panel (D)]. Values are expressed as mean ± standard deviations. *p < 0.01 vs. T0; **p < 0.05 vs. T0; # p < 0.01 vs. no-Cytosorb group; ## p < 0.05 vs. no-Cytosorb group.
FIGURE 5
FIGURE 5
EVLP parameters comparison between Cytosorb and no-Cytosorb group in transplanted grafts [PaO2, panel (A); static and dynamic compliance, panel (B)].
See this image and copyright information in PMC

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