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Title
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Mechanical ventilation impairs IL-17 cytokine family expression in ventilator-associated pneumonia
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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International journal of molecular sciences
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Publication
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2019
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ISSN
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1422-0067
1661-6596
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DOI
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10.3390/IJMS20205072
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Volume/pages
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20
:20
(2019)
, 14 p.
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Article Reference
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5072
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ISI
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000498822800104
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Pubmed ID
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31614857
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Medium
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E-only publicatie
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Full text (Publisher's DOI)
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Full text (open access)
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