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Immune suppression is associated with enhanced systemic inflammatory, endothelial and procoagulant responses in critically ill patients. / Brands, Xanthe; Uhel, Fabrice; van Vught, Lonneke A. et al.

In: PLoS ONE, Vol. 17, No. 7 July, e0271637, 01.07.2022.

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@article{d0d75b4984664a809ca319039a3ab0aa,
title = "Immune suppression is associated with enhanced systemic inflammatory, endothelial and procoagulant responses in critically ill patients",
abstract = "Objective Patients admitted to the Intensive Care Unit (ICU) oftentimes show immunological signs of immune suppression. Consequently, immune stimulatory agents have been proposed as an adjunctive therapy approach in the ICU. The objective of this study was to determine the relationship between the degree of immune suppression and systemic inflammation in patients shortly after admission to the ICU. Design: An observational study in two ICUs in the Netherlands. Methods The capacity of blood leukocytes to produce cytokines upon stimulation with lipopolysaccharide (LPS) was measured in 77 patients on the first morning after ICU admission. Patients were divided in four groups based on quartiles of LPS stimulated tumor necrosis factor (TNF)-α release, reflecting increasing extents of immune suppression. 15 host response biomarkers indicative of aberrations in inflammatory pathways implicated in sepsis pathogenesis were measured in plasma. Results A diminished capacity of blood leukocytes to produce TNF-α upon stimulation with LPS was accompanied by a correspondingly reduced ability to release of IL-1β and IL-6. Concurrently measured plasma concentrations of host response biomarkers demonstrated that the degree of reduction in TNF-α release by blood leukocytes was associated with increasing systemic inflammation, stronger endothelial cell activation, loss of endothelial barrier integrity and enhanced procoagulant responses. Conclusions In patients admitted to the ICU the strongest immune suppression occurs in those who simultaneously display signs of stronger systemic inflammation. These findings may have relevance for the selection of patients eligible for administration of immune enhancing agents.",
author = "Xanthe Brands and Fabrice Uhel and {van Vught}, {Lonneke A.} and Wiewel, {Maryse A.} and Hoogendijk, {Arie J.} and Ren{\'e} Lutter and Schultz, {Marcus J.} and Scicluna, {Brendon P.} and {van der Poll}, Tom",
note = "Funding Information: This research was performed within the framework of the Center for Translational Molecular Medicine (CTMM) (www.ctmm.nl), project Molecular Diagnosis and Risk Stratification of Sepsis (grant 04I-201). The sponsor CTMM was not involved in the design and conduction of the study; nor was the sponsor involved in collection, management, analysis, and interpretation of the data or preparation, review or approval of the article. Decision to submit the article was not dependent on the sponsor. X.B. was supported by a grant from the Netherlands Organization for Health Research and Development (ZonMW #50-53000-98-139). The authors would like to thank the members of the BASIC study group: Friso M. de Beer, Lieuwe D. J. Bos, Gerie J. Glas, Roosmarijn T. M. van Hooijdonk, Janneke Horn, Tom van der Poll, Laura R. A. Schouten, Marcus J. Schultz, Marleen Straat, Lonneke A. van Vught, Luuk Wieske, Maryse A. Wiewel, and Esther Witteveen, as well as all subjects who participated in this study, and Barbara S. Dierdorp and Tamara Dekker for their help with the workup of the cytokine and plasma biomarker measurements. Publisher Copyright: Copyright: {\textcopyright} 2022 Brands et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2022",
month = jul,
day = "1",
doi = "10.1371/journal.pone.0271637",
language = "English",
volume = "17",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7 July",

}

RIS

TY - JOUR

T1 - Immune suppression is associated with enhanced systemic inflammatory, endothelial and procoagulant responses in critically ill patients

AU - Brands, Xanthe

AU - Uhel, Fabrice

AU - van Vught, Lonneke A.

AU - Wiewel, Maryse A.

AU - Hoogendijk, Arie J.

AU - Lutter, René

AU - Schultz, Marcus J.

AU - Scicluna, Brendon P.

AU - van der Poll, Tom

N1 - Funding Information: This research was performed within the framework of the Center for Translational Molecular Medicine (CTMM) (www.ctmm.nl), project Molecular Diagnosis and Risk Stratification of Sepsis (grant 04I-201). The sponsor CTMM was not involved in the design and conduction of the study; nor was the sponsor involved in collection, management, analysis, and interpretation of the data or preparation, review or approval of the article. Decision to submit the article was not dependent on the sponsor. X.B. was supported by a grant from the Netherlands Organization for Health Research and Development (ZonMW #50-53000-98-139). The authors would like to thank the members of the BASIC study group: Friso M. de Beer, Lieuwe D. J. Bos, Gerie J. Glas, Roosmarijn T. M. van Hooijdonk, Janneke Horn, Tom van der Poll, Laura R. A. Schouten, Marcus J. Schultz, Marleen Straat, Lonneke A. van Vught, Luuk Wieske, Maryse A. Wiewel, and Esther Witteveen, as well as all subjects who participated in this study, and Barbara S. Dierdorp and Tamara Dekker for their help with the workup of the cytokine and plasma biomarker measurements. Publisher Copyright: Copyright: © 2022 Brands et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2022/7/1

Y1 - 2022/7/1

N2 - Objective Patients admitted to the Intensive Care Unit (ICU) oftentimes show immunological signs of immune suppression. Consequently, immune stimulatory agents have been proposed as an adjunctive therapy approach in the ICU. The objective of this study was to determine the relationship between the degree of immune suppression and systemic inflammation in patients shortly after admission to the ICU. Design: An observational study in two ICUs in the Netherlands. Methods The capacity of blood leukocytes to produce cytokines upon stimulation with lipopolysaccharide (LPS) was measured in 77 patients on the first morning after ICU admission. Patients were divided in four groups based on quartiles of LPS stimulated tumor necrosis factor (TNF)-α release, reflecting increasing extents of immune suppression. 15 host response biomarkers indicative of aberrations in inflammatory pathways implicated in sepsis pathogenesis were measured in plasma. Results A diminished capacity of blood leukocytes to produce TNF-α upon stimulation with LPS was accompanied by a correspondingly reduced ability to release of IL-1β and IL-6. Concurrently measured plasma concentrations of host response biomarkers demonstrated that the degree of reduction in TNF-α release by blood leukocytes was associated with increasing systemic inflammation, stronger endothelial cell activation, loss of endothelial barrier integrity and enhanced procoagulant responses. Conclusions In patients admitted to the ICU the strongest immune suppression occurs in those who simultaneously display signs of stronger systemic inflammation. These findings may have relevance for the selection of patients eligible for administration of immune enhancing agents.

AB - Objective Patients admitted to the Intensive Care Unit (ICU) oftentimes show immunological signs of immune suppression. Consequently, immune stimulatory agents have been proposed as an adjunctive therapy approach in the ICU. The objective of this study was to determine the relationship between the degree of immune suppression and systemic inflammation in patients shortly after admission to the ICU. Design: An observational study in two ICUs in the Netherlands. Methods The capacity of blood leukocytes to produce cytokines upon stimulation with lipopolysaccharide (LPS) was measured in 77 patients on the first morning after ICU admission. Patients were divided in four groups based on quartiles of LPS stimulated tumor necrosis factor (TNF)-α release, reflecting increasing extents of immune suppression. 15 host response biomarkers indicative of aberrations in inflammatory pathways implicated in sepsis pathogenesis were measured in plasma. Results A diminished capacity of blood leukocytes to produce TNF-α upon stimulation with LPS was accompanied by a correspondingly reduced ability to release of IL-1β and IL-6. Concurrently measured plasma concentrations of host response biomarkers demonstrated that the degree of reduction in TNF-α release by blood leukocytes was associated with increasing systemic inflammation, stronger endothelial cell activation, loss of endothelial barrier integrity and enhanced procoagulant responses. Conclusions In patients admitted to the ICU the strongest immune suppression occurs in those who simultaneously display signs of stronger systemic inflammation. These findings may have relevance for the selection of patients eligible for administration of immune enhancing agents.

UR - http://www.scopus.com/inward/record.url?scp=85135281928&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0271637

DO - 10.1371/journal.pone.0271637

M3 - Article

C2 - 35877767

VL - 17

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 7 July

M1 - e0271637

ER -

ID: 25579291