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Open AccessArticle

Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia

1
Molecular Pathology Group, Laboratory of Cell Biology and Histology, Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium
2
Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium
3
Microbial Sciences, R&D BioPharmaceuticals, AstraZeneca, Gaithersburg, MD 20877, USA
4
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, HP Stratenum 6.131, PO Box 85500, 3508 GA Utrecht, The Netherlands
5
Department of Critical Care Medicine, Antwerp University Hospital and University of Antwerp, LEMP, Wilrijkstraat 10, B-2650 Edegem, Belgium
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(20), 5072; https://doi.org/10.3390/ijms20205072
Received: 30 August 2019 / Revised: 27 September 2019 / Accepted: 8 October 2019 / Published: 12 October 2019
(This article belongs to the Special Issue Lung Diseases and Infections in the New Era)
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 Pseudomonas aeruginosa (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. View Full-Text
Keywords: mechanical ventilation; ventilator-associated pneumonia; VAP; Pseudomonas aeruginosa; IL-17; IL-17A; IL-22; IFNγ mechanical ventilation; ventilator-associated pneumonia; VAP; Pseudomonas aeruginosa; IL-17; IL-17A; IL-22; IFNγ
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De Winter, F.H.R.; ’s Jongers, B.; Bielen, K.; Mancuso, D.; Timbermont, L.; Lammens, C.; Van averbeke, V.; Boddaert, J.; Ali, O.; Kluytmans, J.; Ruzin, A.; Malhotra-Kumar, S.; Jorens, P.G.; Goossens, H.; Kumar-Singh, S. Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia. Int. J. Mol. Sci. 2019, 20, 5072.

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