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Characterization of Circulating IL-10-Producing Cells in Septic Shock Patients: A Proof of Concept Study

Sepsis is a worldwide health priority characterized by the occurrence of severe immunosuppression associated with increased risk of death and secondary infections. Interleukin 10 (IL-10) is a potent immunosuppressive cytokine which plasma concentration is increased in septic patients in association...

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Autores principales: Fabri, Astrid, Kandara, Khalil, Coudereau, Rémy, Gossez, Morgane, Abraham, Paul, Monard, Céline, Cour, Martin, Rimmelé, Thomas, Argaud, Laurent, Monneret, Guillaume, Venet, Fabienne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890231/
https://www.ncbi.nlm.nih.gov/pubmed/33613540
http://dx.doi.org/10.3389/fimmu.2020.615009
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author Fabri, Astrid
Kandara, Khalil
Coudereau, Rémy
Gossez, Morgane
Abraham, Paul
Monard, Céline
Cour, Martin
Rimmelé, Thomas
Argaud, Laurent
Monneret, Guillaume
Venet, Fabienne
author_facet Fabri, Astrid
Kandara, Khalil
Coudereau, Rémy
Gossez, Morgane
Abraham, Paul
Monard, Céline
Cour, Martin
Rimmelé, Thomas
Argaud, Laurent
Monneret, Guillaume
Venet, Fabienne
author_sort Fabri, Astrid
collection PubMed
description Sepsis is a worldwide health priority characterized by the occurrence of severe immunosuppression associated with increased risk of death and secondary infections. Interleukin 10 (IL-10) is a potent immunosuppressive cytokine which plasma concentration is increased in septic patients in association with deleterious outcomes. Despite studies evaluating IL-10 production in specific subpopulations of purified cells, the concomitant description of IL-10 production in monocytes and lymphocytes in septic patients’ whole blood has never been performed. In this pilot study, we characterized IL-10 producing leukocytes in septic shock patients through whole blood intracellular staining by flow cytometry. Twelve adult septic shock patients and 9 healthy volunteers were included. Intracellular tumor necrosis factor-α (TNFα) and IL-10 productions after lipopolysaccharide stimulation by monocytes and IL-10 production after PMA/Ionomycine stimulation by lymphocytes were evaluated. Standard immunomonitoring (HLA-DR expression on monocytes, CD4+ T lymphocyte count) of patients was also performed. TNFα expression by stimulated monocytes was reduced in patients compared with controls while IL-10 production was increased. This was correlated with a reduced monocyte HLA-DR expression. B cells, CD4+, and CD4- T lymphocytes were the three circulating IL-10 producing lymphocyte subsets in both patients and controls. No difference in IL-10 production between patients and controls was observed for B and CD4- T cells. However, IL-10 production by CD4+ T lymphocytes significantly increased in patients in parallel with reduced CD4+ T cells number. Parameters reflecting altered monocyte (increased IL-10 production, decreased HLA-DR expression and decreased TNFα synthesis) and CD4+ T lymphocyte (increased IL-10 production, decreased circulating number) responses were correlated. Using a novel technique for intracellular cytokine measurement in whole blood, our results identify monocytes and CD4+ T cells as the main IL-10 producers in septic patients’ whole blood and illustrate the development of a global immunosuppressive profile in septic shock. Overall, these preliminary results add to our understanding of the global increase in IL-10 production induced by septic shock. Further research is mandatory to determine the pathophysiological mechanisms leading to such increased IL-10 production in monocytes and CD4+ T cells.
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spelling pubmed-78902312021-02-19 Characterization of Circulating IL-10-Producing Cells in Septic Shock Patients: A Proof of Concept Study Fabri, Astrid Kandara, Khalil Coudereau, Rémy Gossez, Morgane Abraham, Paul Monard, Céline Cour, Martin Rimmelé, Thomas Argaud, Laurent Monneret, Guillaume Venet, Fabienne Front Immunol Immunology Sepsis is a worldwide health priority characterized by the occurrence of severe immunosuppression associated with increased risk of death and secondary infections. Interleukin 10 (IL-10) is a potent immunosuppressive cytokine which plasma concentration is increased in septic patients in association with deleterious outcomes. Despite studies evaluating IL-10 production in specific subpopulations of purified cells, the concomitant description of IL-10 production in monocytes and lymphocytes in septic patients’ whole blood has never been performed. In this pilot study, we characterized IL-10 producing leukocytes in septic shock patients through whole blood intracellular staining by flow cytometry. Twelve adult septic shock patients and 9 healthy volunteers were included. Intracellular tumor necrosis factor-α (TNFα) and IL-10 productions after lipopolysaccharide stimulation by monocytes and IL-10 production after PMA/Ionomycine stimulation by lymphocytes were evaluated. Standard immunomonitoring (HLA-DR expression on monocytes, CD4+ T lymphocyte count) of patients was also performed. TNFα expression by stimulated monocytes was reduced in patients compared with controls while IL-10 production was increased. This was correlated with a reduced monocyte HLA-DR expression. B cells, CD4+, and CD4- T lymphocytes were the three circulating IL-10 producing lymphocyte subsets in both patients and controls. No difference in IL-10 production between patients and controls was observed for B and CD4- T cells. However, IL-10 production by CD4+ T lymphocytes significantly increased in patients in parallel with reduced CD4+ T cells number. Parameters reflecting altered monocyte (increased IL-10 production, decreased HLA-DR expression and decreased TNFα synthesis) and CD4+ T lymphocyte (increased IL-10 production, decreased circulating number) responses were correlated. Using a novel technique for intracellular cytokine measurement in whole blood, our results identify monocytes and CD4+ T cells as the main IL-10 producers in septic patients’ whole blood and illustrate the development of a global immunosuppressive profile in septic shock. Overall, these preliminary results add to our understanding of the global increase in IL-10 production induced by septic shock. Further research is mandatory to determine the pathophysiological mechanisms leading to such increased IL-10 production in monocytes and CD4+ T cells. Frontiers Media S.A. 2021-02-04 /pmc/articles/PMC7890231/ /pubmed/33613540 http://dx.doi.org/10.3389/fimmu.2020.615009 Text en Copyright © 2021 Fabri, Kandara, Coudereau, Gossez, Abraham, Monard, Cour, Rimmelé, Argaud, Monneret and Venet http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Fabri, Astrid
Kandara, Khalil
Coudereau, Rémy
Gossez, Morgane
Abraham, Paul
Monard, Céline
Cour, Martin
Rimmelé, Thomas
Argaud, Laurent
Monneret, Guillaume
Venet, Fabienne
Characterization of Circulating IL-10-Producing Cells in Septic Shock Patients: A Proof of Concept Study
title Characterization of Circulating IL-10-Producing Cells in Septic Shock Patients: A Proof of Concept Study
title_full Characterization of Circulating IL-10-Producing Cells in Septic Shock Patients: A Proof of Concept Study
title_fullStr Characterization of Circulating IL-10-Producing Cells in Septic Shock Patients: A Proof of Concept Study
title_full_unstemmed Characterization of Circulating IL-10-Producing Cells in Septic Shock Patients: A Proof of Concept Study
title_short Characterization of Circulating IL-10-Producing Cells in Septic Shock Patients: A Proof of Concept Study
title_sort characterization of circulating il-10-producing cells in septic shock patients: a proof of concept study
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890231/
https://www.ncbi.nlm.nih.gov/pubmed/33613540
http://dx.doi.org/10.3389/fimmu.2020.615009
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