• Thomas Clavier, Marie-Christine Tonon, Anne Foutel, Emmanuel Besnier, Antoine Lefevre-Scelles, Fabrice Morin, Pierrick Gandolfo, Jean-Jacques Tuech, Muriel Quillard, Benoit Veber, Bertrand Dureuil, Hélène Castel, and Vincent Compère.
• 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.
• Crit Care. 2014 Jan 1;18(6):633.

IntroductionRecent 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.MethodsCecal 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.ResultsIn 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.ConclusionsEndozepines might be involved in the inflammatory response in patients with systemic inflammation.

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