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Increased plasma levels of endozepines, endogenous ligands of benzodiazepine receptors, during systemic inflammation: a prospective observational study

INTRODUCTION: Recent work has shown that benzodiazepines interact with the immune system and exhibit anti-inflammatory effects. By using in vitro models, researchers in several studies have shown that the peptidergic endogenous ligands of benzodiazepine receptors, named endozepines, are involved in...

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Autores principales: Clavier, Thomas, Tonon, Marie-Christine, Foutel, Anne, Besnier, Emmanuel, Lefevre-Scelles, Antoine, Morin, Fabrice, Gandolfo, Pierrick, Tuech, Jean-Jacques, Quillard, Muriel, Veber, Benoit, Dureuil, Bertrand, Castel, Hélène, Compère, Vincent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326502/
https://www.ncbi.nlm.nih.gov/pubmed/25407756
http://dx.doi.org/10.1186/s13054-014-0633-7
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author Clavier, Thomas
Tonon, Marie-Christine
Foutel, Anne
Besnier, Emmanuel
Lefevre-Scelles, Antoine
Morin, Fabrice
Gandolfo, Pierrick
Tuech, Jean-Jacques
Quillard, Muriel
Veber, Benoit
Dureuil, Bertrand
Castel, Hélène
Compère, Vincent
author_facet Clavier, Thomas
Tonon, Marie-Christine
Foutel, Anne
Besnier, Emmanuel
Lefevre-Scelles, Antoine
Morin, Fabrice
Gandolfo, Pierrick
Tuech, Jean-Jacques
Quillard, Muriel
Veber, Benoit
Dureuil, Bertrand
Castel, Hélène
Compère, Vincent
author_sort Clavier, Thomas
collection PubMed
description INTRODUCTION: Recent work has shown that benzodiazepines interact with the immune system and exhibit anti-inflammatory effects. By using in vitro models, researchers in several studies have shown that the peptidergic endogenous ligands of benzodiazepine receptors, named endozepines, are involved in the immune response. All endozepines identified so far derive from diazepam-binding inhibitor (DBI), which generates several biologically active fragments. The aim of the present study was to measure plasma levels of DBI-like immunoreactivity (DBI-LI) in a rat model of sepsis and in patients with systemic inflammation from septic or non-septic origin. METHODS: Cecal ligation and puncture (CLP) or sham surgery was performed in rats. Blood samples were taken from animals, patients hospitalized for digestive surgery with inflammatory diseases, and healthy volunteers. Measurements of plasma DBI-related peptides were carried out by radioimmunoassay in animal and human samples. RESULTS: In the rats, CLP provoked an increase of plasma DBI-LI (+37%) 6 hours postsurgery. In humans, DBI-LI levels were significantly higher in the systemic inflammation group than in the healthy volunteer group (48.6 (32.7 to 77.7) pg/ml versus 11.1 (5.9 to 35.3) pg/ml, P < 0.001). We found a positive correlation between endozepine levels and Acute Physiology and Chronic Health Evaluation II score (r(s) = 0.33 (0.026 to 0.58), P < 0.05) and tumor necrosis factor α levels (r(s) = 0.43 (0.14 to 0.65), P < 0.01). The area under the receiver operating characteristic curve for endozepines was 0.842 (95% CI (0.717 to 0.966), P < 0.0001) for discriminating patients with inflammation from healthy volunteers. CONCLUSIONS: Endozepines might be involved in the inflammatory response in patients with systemic inflammation.
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spelling pubmed-43265022015-02-14 Increased plasma levels of endozepines, endogenous ligands of benzodiazepine receptors, during systemic inflammation: a prospective observational study Clavier, Thomas Tonon, Marie-Christine Foutel, Anne Besnier, Emmanuel Lefevre-Scelles, Antoine Morin, Fabrice Gandolfo, Pierrick Tuech, Jean-Jacques Quillard, Muriel Veber, Benoit Dureuil, Bertrand Castel, Hélène Compère, Vincent Crit Care Research INTRODUCTION: Recent work has shown that benzodiazepines interact with the immune system and exhibit anti-inflammatory effects. By using in vitro models, researchers in several studies have shown that the peptidergic endogenous ligands of benzodiazepine receptors, named endozepines, are involved in the immune response. All endozepines identified so far derive from diazepam-binding inhibitor (DBI), which generates several biologically active fragments. The aim of the present study was to measure plasma levels of DBI-like immunoreactivity (DBI-LI) in a rat model of sepsis and in patients with systemic inflammation from septic or non-septic origin. METHODS: Cecal ligation and puncture (CLP) or sham surgery was performed in rats. Blood samples were taken from animals, patients hospitalized for digestive surgery with inflammatory diseases, and healthy volunteers. Measurements of plasma DBI-related peptides were carried out by radioimmunoassay in animal and human samples. RESULTS: In the rats, CLP provoked an increase of plasma DBI-LI (+37%) 6 hours postsurgery. In humans, DBI-LI levels were significantly higher in the systemic inflammation group than in the healthy volunteer group (48.6 (32.7 to 77.7) pg/ml versus 11.1 (5.9 to 35.3) pg/ml, P < 0.001). We found a positive correlation between endozepine levels and Acute Physiology and Chronic Health Evaluation II score (r(s) = 0.33 (0.026 to 0.58), P < 0.05) and tumor necrosis factor α levels (r(s) = 0.43 (0.14 to 0.65), P < 0.01). The area under the receiver operating characteristic curve for endozepines was 0.842 (95% CI (0.717 to 0.966), P < 0.0001) for discriminating patients with inflammation from healthy volunteers. CONCLUSIONS: Endozepines might be involved in the inflammatory response in patients with systemic inflammation. BioMed Central 2014-11-18 2014 /pmc/articles/PMC4326502/ /pubmed/25407756 http://dx.doi.org/10.1186/s13054-014-0633-7 Text en © Clavier et al.; licensee BioMed Central. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Clavier, Thomas
Tonon, Marie-Christine
Foutel, Anne
Besnier, Emmanuel
Lefevre-Scelles, Antoine
Morin, Fabrice
Gandolfo, Pierrick
Tuech, Jean-Jacques
Quillard, Muriel
Veber, Benoit
Dureuil, Bertrand
Castel, Hélène
Compère, Vincent
Increased plasma levels of endozepines, endogenous ligands of benzodiazepine receptors, during systemic inflammation: a prospective observational study
title Increased plasma levels of endozepines, endogenous ligands of benzodiazepine receptors, during systemic inflammation: a prospective observational study
title_full Increased plasma levels of endozepines, endogenous ligands of benzodiazepine receptors, during systemic inflammation: a prospective observational study
title_fullStr Increased plasma levels of endozepines, endogenous ligands of benzodiazepine receptors, during systemic inflammation: a prospective observational study
title_full_unstemmed Increased plasma levels of endozepines, endogenous ligands of benzodiazepine receptors, during systemic inflammation: a prospective observational study
title_short Increased plasma levels of endozepines, endogenous ligands of benzodiazepine receptors, during systemic inflammation: a prospective observational study
title_sort increased plasma levels of endozepines, endogenous ligands of benzodiazepine receptors, during systemic inflammation: a prospective observational study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326502/
https://www.ncbi.nlm.nih.gov/pubmed/25407756
http://dx.doi.org/10.1186/s13054-014-0633-7
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