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      Neutrophil expression of glucocorticoid-induced leucine zipper (GILZ) anti-inflammatory protein is associated with acute respiratory distress syndrome severity

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          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.


          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).


          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.


          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.

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          Most cited references 36

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          A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study.

          To develop and validate a new Simplified Acute Physiology Score, the SAPS II, from a large sample of surgical and medical patients, and to provide a method to convert the score to a probability of hospital mortality. The SAPS II and the probability of hospital mortality were developed and validated using data from consecutive admissions to 137 adult medical and/or surgical intensive care units in 12 countries. The 13,152 patients were randomly divided into developmental (65%) and validation (35%) samples. Patients younger than 18 years, burn patients, coronary care patients, and cardiac surgery patients were excluded. Vital status at hospital discharge. The SAPS II includes only 17 variables: 12 physiology variables, age, type of admission (scheduled surgical, unscheduled surgical, or medical), and three underlying disease variables (acquired immunodeficiency syndrome, metastatic cancer, and hematologic malignancy). Goodness-of-fit tests indicated that the model performed well in the developmental sample and validated well in an independent sample of patients (P = .883 and P = .104 in the developmental and validation samples, respectively). The area under the receiver operating characteristic curve was 0.88 in the developmental sample and 0.86 in the validation sample. The SAPS II, based on a large international sample of patients, provides an estimate of the risk of death without having to specify a primary diagnosis. This is a starting point for future evaluation of the efficiency of intensive care units.
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            An expanded definition of the adult respiratory distress syndrome.

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              NET balancing: a problem in inflammatory lung diseases

              Neutrophil extracellular traps (NETs) are beneficial antimicrobial defense structures that can help fight against invading pathogens in the host. However, recent studies reveal that NETs exert adverse effects in a number of diseases including those of the lung. Many inflammatory lung diseases are characterized with a massive influx of neutrophils into the airways. Neutrophils contribute to the pathology of these diseases. To date, NETs have been identified in the lungs of cystic fibrosis (CF), acute lung injury (ALI), allergic asthma, and lungs infected with bacteria, virus, or fungi. These microbes and several host factors can stimulate NET formation, or NETosis. Different forms of NETosis have been identified and are dependent on varying types of stimuli. All of these pathways however appear to result in the formation of NETs that contain DNA, modified extracellular histones, proteases, and cytotoxic enzymes. Some of the NET components are immunogenic and damaging to host tissue. Innate immune collectins, such as pulmonary surfactant protein D (SP-D), bind NETs, and enhance the clearance of dying cells and DNA by alveolar macrophages. In many inflammatory lung diseases, bronchoalveolar SP-D levels are altered and its deficiency results in the accumulation of DNA in the lungs. Some of the other therapeutic molecules under consideration for treating NET-related diseases include DNases, antiproteases, myeloperoxidase (MPO) inhibitors, peptidylarginine deiminase-4 inhibitors, and anti-histone antibodies. NETs could provide important biological advantage for the host to fight against certain microbial infections. However, too much of a good thing can be a bad thing. Maintaining the right balance of NET formation and reducing the amount of NETs that accumulate in tissues are essential for harnessing the power of NETs with minimal damage to the hosts.

                Author and article information

                33-1 46 83 59 80 , armelle.biola-vidamment@u-psud.fr
                Ann Intensive Care
                Ann Intensive Care
                Annals of Intensive Care
                Springer Paris (Paris )
                2 November 2016
                2 November 2016
                : 6
                [1 ]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
                [2 ]Département d’Anesthésie-Réanimation, Hôpital Bichat-Claude Bernard, AP-HP, Paris, France
                [3 ]Université Paris Diderot, Sorbonne Paris Cité, Paris, France
                [4 ]Département d’Epidémiologie et Recherche Clinique, Assistance Publique-Hôpitaux de Paris Hôpital Bichat, INSERM, CIE 801, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
                [5 ]Laboratoire d’immunologie, «Autoimmunité et hypersensibilités», Hôpital Bichat-Claude Bernard, AP-HP, Paris, France
                © The Author(s) 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                Funded by: INSERM institutional grants
                Funded by: Fondation du souffle et Fond de dotation pour la recherche en santé respiratoire
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