Abstract
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).ResultsNeutrophil 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.
Highlights
Glucocorticoid-induced leucine zipper (GILZ) is a potent anti-inflammatory protein involved in neutro‐ phil apoptosis and the resolution of inflammation
The acute respiratory distress syndrome (ARDS) patients stayed longer in the intensive care unit (ICU) than the controls, allowing serial blood sampling for GILZ analysis
The gilz gene is transiently expressed by blood neutrophils from ARDS patients, which depends on corticosteroids but not on vasoactive agent administration Neutrophil gilz expression was transiently detected in several ARDS patients (9/17) but only in few controls (2/14)
Summary
Glucocorticoid-induced leucine zipper (GILZ) is a potent anti-inflammatory protein involved in neutro‐ phil apoptosis and the resolution of inflammation. Steroids have controversial effects when used early during the course of ARDS [9], but have been shown to reduce fibroblast proliferation and cytokine release when used in the late phase, thereby improving recovery [10]. Another effect of steroid therapy might be the induction of glucocorticoid-induced leucine zipper (GILZ). GILZ can be induced in vitro by TGF-β and IL-10 [12], and has been detected both in a murine model of arthritis and in the joints of patients with rheumatoid arthritis [13] These recent in vivo findings suggest that, in some inflammatory conditions, GILZ may be induced independent from exogenous corticosteroid administration
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