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Anaesthesia Critical Care & Pain Medicine
Sous presse. Epreuves corrigées par l'auteur. Disponible en ligne depuis le vendredi 8 mars 2019
Doi : 10.1016/j.accpm.2019.01.009
Low interleukin-10 release after ex vivo stimulation of whole blood is associated with persistent organ dysfunction in sepsis: A prospective observational study
 

Nicolas Nesseler a, b, c, d, , Corinne Martin-Chouly b, e, Harmonie Perrichet a, b, James T. Ross f, Chloé Rousseau d, Pratik Sinha g, Sonia Isslame a, Elodie Masseret a, Yannick Mallédant a, b, c, Yoann Launey a, b, c, Philippe Seguin a, b, c, d
a Intensive care unit, anaesthesia and critical care department, Pontchaillou, university hospital of Rennes, 35000 Rennes, France 
b Rennes 1 university, Rennes, France 
c Inserm, UMR 1214 NuMeCan, Pontchaillou, university hospital of Rennes, 35000 Rennes, France 
d Clinical investigation centre, inserm unit 1414, Pontchaillou, university hospital of Rennes, 35000 Rennes, France 
e Inserm, UMR 1085 IRSET, research institute for environmental and occupational health, Rennes, France 
f Department of surgery, university of California, San Francisco, USA 
g Department of medicine and anesthesia, division of pulmonary and critical care, university of California, San Francisco, USA 

Corresponding author at: Hôpital Pontchaillou, pôle anesthésie, SAMU, urgences, réanimations, médecine interne et gériatrie (ASUR-MIG), 2, rue Henri Le Guilloux, 35033 Rennes cedex 9, France.Hôpital Pontchailloupôle anesthésieSAMU, urgences, réanimations, médecine interne et gériatrie (ASUR-MIG)2, rue Henri Le GuillouxRennes cedex 935033France
Abstract
Background

Sepsis profoundly alters immune homeostasis. Cytokine release after whole blood lipopolysaccharide (LPS)-stimulation reflects cell function across multiple immune cell classes and represents the immune response to LPS. The main goal of this study was to evaluate the prognostic value of ex vivo stimulation of whole blood with LPS in sepsis.

Methods

Blood was drawn on day 1 and day 7 after admission, and stimulated ex vivo with LPS. Tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 were measured with and without stimulation. Our primary outcome measure was the persistence of at least one organ dysfunction at day 7. Organ dysfunction was defined according to the SOFA components by a score ≥ 2.

Results

Forty-nine patients with sepsis from a 21-bed intensive care unit, and 23 healthy volunteers were enrolled. The blood of septic patients was less responsive to ex vivo stimulation with LPS than that of healthy controls at day 1 and 7, as demonstrated by lower TNF-α, IL-1β, IL-6 and IL-10 release. Persistent organ dysfunction was more frequent in patients with lower IL-10 release at day 1 but such an association was not found for pro-inflammatory cytokines. A persistent low IL-10 release at day 7 was also associated with persistent organ dysfunction.

Conclusion

These data suggest that the capacity to produce IL-10 in response to whole blood ex vivo stimulation early in sepsis, as well as persistent low IL-10 response over time, may help in prognostication and patient stratification. These results will need to be confirmed in future studies.

The full text of this article is available in PDF format.

Keywords : Prognosis, Immunosuppression, SOFA score, Lipopolysaccharide, Endotoxin, Cytokines




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