Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia
Mechanical ventilation (MV) is the primary risk factor for the development of ventilator-associated pneumonia (VAP). Besides inducing a pro-inflammatory T-helper (Th)-1 cytokine response, MV also induces an anti-inflammatory Th2 cytokine response, marked by increased IL-4 secretion and reduced bacte...
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MDPI AG
2019-10-01
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Series: | International Journal of Molecular Sciences |
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Online Access: | https://www.mdpi.com/1422-0067/20/20/5072 |
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doaj-8236e7f16d1c4897a58d6d7391e8c440 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fien H. R. De Winter Bart ’s Jongers Kenny Bielen Domenico Mancuso Leen Timbermont Christine Lammens Vincent Van averbeke Jan Boddaert Omar Ali Jan Kluytmans Alexey Ruzin Surbhi Malhotra-Kumar Philippe G. Jorens Herman Goossens Samir Kumar-Singh |
spellingShingle |
Fien H. R. De Winter Bart ’s Jongers Kenny Bielen Domenico Mancuso Leen Timbermont Christine Lammens Vincent Van averbeke Jan Boddaert Omar Ali Jan Kluytmans Alexey Ruzin Surbhi Malhotra-Kumar Philippe G. Jorens Herman Goossens Samir Kumar-Singh Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia International Journal of Molecular Sciences mechanical ventilation ventilator-associated pneumonia vap <i>pseudomonas aeruginosa</i> il-17 il-17a il-22 ifnγ |
author_facet |
Fien H. R. De Winter Bart ’s Jongers Kenny Bielen Domenico Mancuso Leen Timbermont Christine Lammens Vincent Van averbeke Jan Boddaert Omar Ali Jan Kluytmans Alexey Ruzin Surbhi Malhotra-Kumar Philippe G. Jorens Herman Goossens Samir Kumar-Singh |
author_sort |
Fien H. R. De Winter |
title |
Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia |
title_short |
Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia |
title_full |
Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia |
title_fullStr |
Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia |
title_full_unstemmed |
Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia |
title_sort |
mechanical ventilation impairs il-17 cytokine family expression in ventilator-associated pneumonia |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-10-01 |
description |
Mechanical ventilation (MV) is the primary risk factor for the development of ventilator-associated pneumonia (VAP). Besides inducing a pro-inflammatory T-helper (Th)-1 cytokine response, MV also induces an anti-inflammatory Th2 cytokine response, marked by increased IL-4 secretion and reduced bacterial phagocytic capacity of rodent lung macrophages. Since IL-4 is known to downregulate both Th1 and Th17 cytokines, the latter is important in mediating mucosal immunity and combating bacterial and fungal growth, we studied and showed here in a rat model of MV that Th17 cytokines (IL-17A, IL-17F, and IL-22) were significantly upregulated in the lung as a response to different MV strategies currently utilized in clinic. To study whether the increased IL-4 levels are associated with downregulation of the anti-bacterial Th17 cytokines, we subsequently challenged mechanically ventilated rats with an intratracheal inoculation of <i>Pseudomonas aeruginosa</i> (VAP model) and showed a dramatic downregulation of IL-17A, IL-17F, and IL-22, compared to animals receiving the same bacterial burden without MV. For the studied Th1 cytokines (IFNγ, TNFα, IL-6, and IL-1β), only IFNγ showed a significant decrease as a consequence of bacterial infection in mechanically ventilated rats. We further studied IL-17A, the most studied IL-17 family member, in intensive care unit (ICU) pneumonia patients and showed that VAP patients had significantly lower levels of IL-17A in the endotracheal aspirate compared to patients entering ICU with pre-existing pneumonia. These translational data, obtained both in animal models and in humans, suggest that a deficient anti-bacterial Th17 response in the lung during MV is associated with VAP development. |
topic |
mechanical ventilation ventilator-associated pneumonia vap <i>pseudomonas aeruginosa</i> il-17 il-17a il-22 ifnγ |
url |
https://www.mdpi.com/1422-0067/20/20/5072 |
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doaj-8236e7f16d1c4897a58d6d7391e8c4402020-11-25T01:44:04ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-10-012020507210.3390/ijms20205072ijms20205072Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated PneumoniaFien H. R. De Winter0Bart ’s Jongers1Kenny Bielen2Domenico Mancuso3Leen Timbermont4Christine Lammens5Vincent Van averbeke6Jan Boddaert7Omar Ali8Jan Kluytmans9Alexey Ruzin10Surbhi Malhotra-Kumar11Philippe G. Jorens12Herman Goossens13Samir Kumar-Singh14Molecular Pathology Group, Laboratory of Cell Biology and Histology, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, BelgiumMolecular Pathology Group, Laboratory of Cell Biology and Histology, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, BelgiumMolecular Pathology Group, Laboratory of Cell Biology and Histology, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, BelgiumMolecular Pathology Group, Laboratory of Cell Biology and Histology, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, BelgiumLaboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, BelgiumLaboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, BelgiumMolecular Pathology Group, Laboratory of Cell Biology and Histology, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, BelgiumMolecular Pathology Group, Laboratory of Cell Biology and Histology, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, BelgiumMicrobial Sciences, R&D BioPharmaceuticals, AstraZeneca, Gaithersburg, MD 20877, USAJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, HP Stratenum 6.131, PO Box 85500, 3508 GA Utrecht, The NetherlandsMicrobial Sciences, R&D BioPharmaceuticals, AstraZeneca, Gaithersburg, MD 20877, USALaboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, BelgiumDepartment of Critical Care Medicine, Antwerp University Hospital and University of Antwerp, LEMP, Wilrijkstraat 10, B-2650 Edegem, BelgiumLaboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, BelgiumMolecular Pathology Group, Laboratory of Cell Biology and Histology, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, BelgiumMechanical ventilation (MV) is the primary risk factor for the development of ventilator-associated pneumonia (VAP). Besides inducing a pro-inflammatory T-helper (Th)-1 cytokine response, MV also induces an anti-inflammatory Th2 cytokine response, marked by increased IL-4 secretion and reduced bacterial phagocytic capacity of rodent lung macrophages. Since IL-4 is known to downregulate both Th1 and Th17 cytokines, the latter is important in mediating mucosal immunity and combating bacterial and fungal growth, we studied and showed here in a rat model of MV that Th17 cytokines (IL-17A, IL-17F, and IL-22) were significantly upregulated in the lung as a response to different MV strategies currently utilized in clinic. To study whether the increased IL-4 levels are associated with downregulation of the anti-bacterial Th17 cytokines, we subsequently challenged mechanically ventilated rats with an intratracheal inoculation of <i>Pseudomonas aeruginosa</i> (VAP model) and showed a dramatic downregulation of IL-17A, IL-17F, and IL-22, compared to animals receiving the same bacterial burden without MV. For the studied Th1 cytokines (IFNγ, TNFα, IL-6, and IL-1β), only IFNγ showed a significant decrease as a consequence of bacterial infection in mechanically ventilated rats. We further studied IL-17A, the most studied IL-17 family member, in intensive care unit (ICU) pneumonia patients and showed that VAP patients had significantly lower levels of IL-17A in the endotracheal aspirate compared to patients entering ICU with pre-existing pneumonia. These translational data, obtained both in animal models and in humans, suggest that a deficient anti-bacterial Th17 response in the lung during MV is associated with VAP development.https://www.mdpi.com/1422-0067/20/20/5072mechanical ventilationventilator-associated pneumoniavap<i>pseudomonas aeruginosa</i>il-17il-17ail-22ifnγ |