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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829394/ https://www.ncbi.nlm.nih.gov/pubmed/31614857 http://dx.doi.org/10.3390/ijms20205072 |
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author | De Winter, Fien H. R. ’s Jongers, Bart Bielen, Kenny Mancuso, Domenico Timbermont, Leen Lammens, Christine Van averbeke, Vincent Boddaert, Jan Ali, Omar Kluytmans, Jan Ruzin, Alexey Malhotra-Kumar, Surbhi Jorens, Philippe G. Goossens, Herman Kumar-Singh, Samir |
author_facet | De Winter, Fien H. R. ’s Jongers, Bart Bielen, Kenny Mancuso, Domenico Timbermont, Leen Lammens, Christine Van averbeke, Vincent Boddaert, Jan Ali, Omar Kluytmans, Jan Ruzin, Alexey Malhotra-Kumar, Surbhi Jorens, Philippe G. Goossens, Herman Kumar-Singh, Samir |
author_sort | De Winter, Fien H. R. |
collection | PubMed |
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 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. |
format | Online Article Text |
id | pubmed-6829394 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68293942019-11-18 Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia De Winter, Fien H. R. ’s Jongers, Bart Bielen, Kenny Mancuso, Domenico Timbermont, Leen Lammens, Christine Van averbeke, Vincent Boddaert, Jan Ali, Omar Kluytmans, Jan Ruzin, Alexey Malhotra-Kumar, Surbhi Jorens, Philippe G. Goossens, Herman Kumar-Singh, Samir Int J Mol Sci Article 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. MDPI 2019-10-12 /pmc/articles/PMC6829394/ /pubmed/31614857 http://dx.doi.org/10.3390/ijms20205072 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article De Winter, Fien H. R. ’s Jongers, Bart Bielen, Kenny Mancuso, Domenico Timbermont, Leen Lammens, Christine Van averbeke, Vincent Boddaert, Jan Ali, Omar Kluytmans, Jan Ruzin, Alexey Malhotra-Kumar, Surbhi Jorens, Philippe G. Goossens, Herman Kumar-Singh, Samir Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia |
title | 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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829394/ https://www.ncbi.nlm.nih.gov/pubmed/31614857 http://dx.doi.org/10.3390/ijms20205072 |
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