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Crit Care. 2014 Nov 18;18(6):633. doi: 10.1186/s13054-014-0633-7.

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

Clavier T1,2,3,4, Tonon MC5,6,7, Foutel A8, Besnier E9,10,11,12, Lefevre-Scelles A13, Morin F14,15,16, Gandolfo P17,18,19, Tuech JJ20, Quillard M21, Veber B22, Dureuil B23, Castel H24,25,26, Compère V27,28,29,30.

Author information

1
Institut National de la Santé et de la Recherche Médicale (Inserm), U982, Place Emile Blondel, 76130, Mont-Saint-Aignan, France. thomas.clavier@chu-rouen.fr.
2
Normandy University, Institute for Research and Innovation in Biomedicine (IRIB), Place Emile Blondel, 76130, Mont-Saint-Aignan, France. thomas.clavier@chu-rouen.fr.
3
Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Place Emile Blondel, 76130, Mont-Saint-Aignan, France. thomas.clavier@chu-rouen.fr.
4
Department of Anesthesiology and Critical Care, Rouen University Hospital, Rue de Germont, 76000, Rouen, France. thomas.clavier@chu-rouen.fr.
5
Institut National de la Santé et de la Recherche Médicale (Inserm), U982, Place Emile Blondel, 76130, Mont-Saint-Aignan, France. marie-christine.tonon@univ-rouen.fr.
6
Normandy University, Institute for Research and Innovation in Biomedicine (IRIB), Place Emile Blondel, 76130, Mont-Saint-Aignan, France. marie-christine.tonon@univ-rouen.fr.
7
Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Place Emile Blondel, 76130, Mont-Saint-Aignan, France. marie-christine.tonon@univ-rouen.fr.
8
Department of Anesthesiology and Critical Care, Rouen University Hospital, Rue de Germont, 76000, Rouen, France. anne.foutel@chu-rouen.fr.
9
Institut National de la Santé et de la Recherche Médicale (Inserm), U982, Place Emile Blondel, 76130, Mont-Saint-Aignan, France. emmanuel.besnier@chu-rouen.fr.
10
Normandy University, Institute for Research and Innovation in Biomedicine (IRIB), Place Emile Blondel, 76130, Mont-Saint-Aignan, France. emmanuel.besnier@chu-rouen.fr.
11
Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Place Emile Blondel, 76130, Mont-Saint-Aignan, France. emmanuel.besnier@chu-rouen.fr.
12
Department of Anesthesiology and Critical Care, Rouen University Hospital, Rue de Germont, 76000, Rouen, France. emmanuel.besnier@chu-rouen.fr.
13
Department of Anesthesiology and Critical Care, Rouen University Hospital, Rue de Germont, 76000, Rouen, France. antoine.lefevre-scelles@chu-rouen.fr.
14
Institut National de la Santé et de la Recherche Médicale (Inserm), U982, Place Emile Blondel, 76130, Mont-Saint-Aignan, France. fabrice.morin@univ-rouen.fr.
15
Normandy University, Institute for Research and Innovation in Biomedicine (IRIB), Place Emile Blondel, 76130, Mont-Saint-Aignan, France. fabrice.morin@univ-rouen.fr.
16
Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Place Emile Blondel, 76130, Mont-Saint-Aignan, France. fabrice.morin@univ-rouen.fr.
17
Institut National de la Santé et de la Recherche Médicale (Inserm), U982, Place Emile Blondel, 76130, Mont-Saint-Aignan, France. pierrick.gandolfo@univ-rouen.fr.
18
Normandy University, Institute for Research and Innovation in Biomedicine (IRIB), Place Emile Blondel, 76130, Mont-Saint-Aignan, France. pierrick.gandolfo@univ-rouen.fr.
19
Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Place Emile Blondel, 76130, Mont-Saint-Aignan, France. pierrick.gandolfo@univ-rouen.fr.
20
Department of Digestive Surgery, Rouen University Hospital, Rue de Germont, 76000, Rouen, France. jean-jacques.tuech@chu-rouen.fr.
21
Department of Medical Biochemistry, Institute of Clinical Biology, Rouen University Hospital, 76000, Rouen, France. muriel.quillard@chu-rouen.fr.
22
Department of Anesthesiology and Critical Care, Rouen University Hospital, Rue de Germont, 76000, Rouen, France. benoit.veber@chu-rouen.fr.
23
Department of Anesthesiology and Critical Care, Rouen University Hospital, Rue de Germont, 76000, Rouen, France. bertrand.dureuil@chu-rouen.fr.
24
Institut National de la Santé et de la Recherche Médicale (Inserm), U982, Place Emile Blondel, 76130, Mont-Saint-Aignan, France. helene.castel@univ-rouen.fr.
25
Normandy University, Institute for Research and Innovation in Biomedicine (IRIB), Place Emile Blondel, 76130, Mont-Saint-Aignan, France. helene.castel@univ-rouen.fr.
26
Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Place Emile Blondel, 76130, Mont-Saint-Aignan, France. helene.castel@univ-rouen.fr.
27
Institut National de la Santé et de la Recherche Médicale (Inserm), U982, Place Emile Blondel, 76130, Mont-Saint-Aignan, France. vincent.compere@chu-rouen.fr.
28
Normandy University, Institute for Research and Innovation in Biomedicine (IRIB), Place Emile Blondel, 76130, Mont-Saint-Aignan, France. vincent.compere@chu-rouen.fr.
29
Rouen University, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Place Emile Blondel, 76130, Mont-Saint-Aignan, France. vincent.compere@chu-rouen.fr.
30
Department of Anesthesiology and Critical Care, Rouen University Hospital, Rue de Germont, 76000, Rouen, France. vincent.compere@chu-rouen.fr.

Abstract

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 <  .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.

PMID:
25407756
PMCID:
PMC4326502
DOI:
10.1186/s13054-014-0633-7
[Indexed for MEDLINE]
Free PMC Article

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