Neutrophil expression of glucocorticoid-induced leucine zipper (GILZ) anti-inflammatory protein is associated with acute respiratory distress syndrome severity.
BACKGROUND
Glucocorticoid-induced leucine zipper (GILZ) is a potent anti-inflammatory protein involved in neutrophil apoptosis and the resolution of inflammation. Given the numerous pathophysiologic roles of neutrophils in the acute respiratory distress syndrome (ARDS), we postulated that neutrophil GILZ expression might be induced during ARDS, to modulate the inflammatory process and participate in lung repair.


METHODS
This single-center, prospective, observational cohort study took place in the surgical intensive care unit of Bichat Hospital (Paris, France) and involved 17 ARDS patients meeting the Berlin criteria at inclusion, and 14 ventilated controls without ARDS. Serial blood samples were obtained every 2 days until extubation or death (from 1 to 9 samples per patient). GILZ protein and gene expression was quantified in blood neutrophils, along with markers of inflammation (CRP, extracellular DNA) or its resolution (Annexin A1).


RESULTS
Neutrophil GILZ expression was detected at the transcriptional and/or translational level in 9/17 ARDS patients (in particular 7/10 severe ARDS) and in 2/14 ventilated controls. The highest mRNA levels were observed in the most severely ill patients (p < 0.028). GILZ was expressed in about ¾ of the corticosteroid-treated patients and its expression could also occur independently of corticosteroids, suggesting that inflammatory signals may also induce neutrophil GILZ expression in vivo.


CONCLUSIONS
In this pilot study, we show for the first time that blood neutrophils from patients with ARDS can express GILZ, in keeping with an anti-inflammatory and regulatory endogenous role of GILZ in humans. Contrary to some markers of inflammation or its resolution, the levels of gilz gene expression were related to ARDS severity.
INSERM UMR-996 - Inflammation, Chemokines and Immunopathology, Univ Paris-Sud, Faculté de pharmacie, Université Paris-Saclay, 5 rue JB Clément, 92296, Châtenay-Malabry Cedex, France.
Marie-Alix
MA
Espinasse
Département d'Epidémiologie et Recherche Clinique, Assistance Publique-Hôpitaux de Paris Hôpital Bichat, INSERM, CIE 801, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
David
D
Hajage
Département d'Anesthésie-Réanimation, Hôpital Bichat-Claude Bernard, AP-HP, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Philippe
P
Montravers
Département d'Anesthésie-Réanimation, Hôpital Bichat-Claude Bernard, AP-HP, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Pascale
P
Piednoir
Département d'Anesthésie-Réanimation, Hôpital Bichat-Claude Bernard, AP-HP, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Guillaume
G
Dufour
Département d'Epidémiologie et Recherche Clinique, Assistance Publique-Hôpitaux de Paris Hôpital Bichat, INSERM, CIE 801, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Florence
F
Tubach
INSERM UMR-996 - Inflammation, Chemokines and Immunopathology, Univ Paris-Sud, Faculté de pharmacie, Université Paris-Saclay, 5 rue JB Clément, 92296, Châtenay-Malabry Cedex, France.|Laboratoire d'immunologie, «Autoimmunité et hypersensibilités», Hôpital Bichat-Claude Bernard, AP-HP, Paris, France.
Vanessa
V
Granger
INSERM UMR-996 - Inflammation, Chemokines and Immunopathology, Univ Paris-Sud, Faculté de pharmacie, Université Paris-Saclay, 5 rue JB Clément, 92296, Châtenay-Malabry Cedex, France.|Laboratoire d'immunologie, «Autoimmunité et hypersensibilités», Hôpital Bichat-Claude Bernard, AP-HP, Paris, France.
Luc
L
de Chaisemartin
INSERM UMR-996 - Inflammation, Chemokines and Immunopathology, Univ Paris-Sud, Faculté de pharmacie, Université Paris-Saclay, 5 rue JB Clément, 92296, Châtenay-Malabry Cedex, France.
Benoît
B
Noël
INSERM UMR-996 - Inflammation, Chemokines and Immunopathology, Univ Paris-Sud, Faculté de pharmacie, Université Paris-Saclay, 5 rue JB Clément, 92296, Châtenay-Malabry Cedex, France.
Marc
M
Pallardy
INSERM UMR-996 - Inflammation, Chemokines and Immunopathology, Univ Paris-Sud, Faculté de pharmacie, Université Paris-Saclay, 5 rue JB Clément, 92296, Châtenay-Malabry Cedex, France.|Laboratoire d'immunologie, «Autoimmunité et hypersensibilités», Hôpital Bichat-Claude Bernard, AP-HP, Paris, France.
Sylvie
S
Chollet-Martin
INSERM UMR-996 - Inflammation, Chemokines and Immunopathology, Univ Paris-Sud, Faculté de pharmacie, Université Paris-Saclay, 5 rue JB Clément, 92296, Châtenay-Malabry Cedex, France. armelle.biola-vidamment@u-psud.fr.
Armelle
http://orcid.org/0000-0003-1113-5851
A
Biola-Vidamment
ARDS; Annexin A1; Extracellular DNA; Glucocorticoid-induced leucine zipper (GILZ); Neutrophils