Circulating CXCL10 and IL-6 in solid organ donors after brain death predict graft outcomes

Lorenzo Piemonti,Lorenzo Piemonti,Andrea Gianelli Castiglione,Valeria Sordi,Valeria Sordi,Silvia Pellegrini,Silvia Pellegrini,Marina Scavini,Marina Scavini,Massimo Cardillo,Viviana Sioli,Giulia Maria Scotti

doi:10.1038/s41598-021-86085-6

Abstract

We tested the hypothesis that circulating CXCL10 and IL-6 in donor after brain death provide independent additional predictors of graft outcome. From January 1, 2010 to June 30, 2012 all donors after brain death managed by the NITp (n = 1100) were prospectively included in this study. CXCL10 and IL-6 were measured on serum collected for the crossmatch at the beginning of the observation period. Graft outcome in recipients who received kidney (n = 1325, follow-up 4.9 years), liver (n = 815, follow-up 4.3 years) and heart (n = 272, follow-up 5 years) was evaluated. Both CXCL-10 and IL-6 showed increased concentration in donors after brain death. The intensive care unit stay, the hemodynamic instability, the cause of death, the presence of risk factors for cardiovascular disease and the presence of ongoing infection resulted as significant determinants of IL-6 and CXCL10 donor concentrations. Both cytokines resulted as independent predictors of Immediate Graft Function. Donor IL-6 or CXCL10 were associated with graft failure after liver transplant, and acted as predictors of recipient survival after kidney, liver and heart transplantation. Serum donor IL-6 and CXCL10 concentration can provide independent incremental prediction of graft outcome among recipients followed according to standard clinical practice.

Highlights

We tested the hypothesis that circulating CXCL10 and IL-6 in donor after brain death provide independent additional predictors of graft outcome
A higher percentage of infections as cause of death was observed after heart transplant in high IL-6/ CXCL10 category. This is the largest prospective study examining whether the inflammatory status of the donor after brain death provides independent additional prediction of graft outcome among recipients followed according to standard clinical practice
Experiments in animal models have previously demonstrated the relation between brain death and the rapid infiltration of leukocyte populations in peripheral organs with intense upregulation of their associated p roducts[14]

Summary

Introduction

We tested the hypothesis that circulating CXCL10 and IL-6 in donor after brain death provide independent additional predictors of graft outcome. Whereas early immune-mediated injury is primarily responsible for graft dysfunction and failure, the influence of antigen-independent events may have been underestimated This concept is supported by data showing similar survival rates for kidneys from living-unrelated donors and one-haplotype matched living-related d onors[7,8,9]. Organs from donors after brain death that are transplanted into unmodified allogeneic hosts experience function loss at an accelerated rate compared to those from living d onors[22,23] This concept is supported by the clinical finding of a consistently inferior outcome (i.e., function and survival) of kidney allografts with delayed function plus acute rejection compared to organs with a single insult or no insult at a ll[24,25,26,27]. We focused our analysis on these two immunological mediators because they have a common double advantage: to be extremely relevant for the immune response after transplantation and to be the target of drugs already available on the market (i.e., Tocilizumab, Sarilumab) or in advanced experimental clinical phases in humans (i.e., Eldelumab) (45)(46)

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