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IL-1β processing in mechanical ventilation-induced inflammation is dependent on neutrophil factors rather than caspase-1

PURPOSE: Mechanical ventilation can cause ventilator-induced lung injury, characterized by a sterile inflammatory response in the lungs resulting in tissue damage and respiratory failure. The cytokine interleukin-1β (IL-1β) is thought to play an important role in the pathogenesis of ventilator-induc...

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Autores principales: Timmermans, Kim, van der Wal, Selina EI, Vaneker, Michiel, van der Laak, Jeroen AWM, Netea, Mihai G, Pickkers, Peter, Scheffer, Gert Jan, Joosten, Leo AB, Kox, Matthijs
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797957/
https://www.ncbi.nlm.nih.gov/pubmed/26266796
http://dx.doi.org/10.1186/2197-425X-1-8
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author Timmermans, Kim
van der Wal, Selina EI
Vaneker, Michiel
van der Laak, Jeroen AWM
Netea, Mihai G
Pickkers, Peter
Scheffer, Gert Jan
Joosten, Leo AB
Kox, Matthijs
author_facet Timmermans, Kim
van der Wal, Selina EI
Vaneker, Michiel
van der Laak, Jeroen AWM
Netea, Mihai G
Pickkers, Peter
Scheffer, Gert Jan
Joosten, Leo AB
Kox, Matthijs
author_sort Timmermans, Kim
collection PubMed
description PURPOSE: Mechanical ventilation can cause ventilator-induced lung injury, characterized by a sterile inflammatory response in the lungs resulting in tissue damage and respiratory failure. The cytokine interleukin-1β (IL-1β) is thought to play an important role in the pathogenesis of ventilator-induced lung injury. Cleavage of the inactive precursor pro-IL-1β to form bioactive IL-1β is mediated by several types of proteases, of which caspase-1, activated within the inflammasome, is the most important. Herein, we studied the roles of IL-1β, caspase-1 and neutrophil factors in the mechanical ventilation-induced inflammatory response in mice. METHODS: Untreated wild-type mice, IL-1αβ knockout and caspase-1 knockout mice, pralnacasan (a selective caspase-1 inhibitor)-treated mice, anti-keratinocyte-derived chemokine (KC)-treated mice and cyclophosphamide-treated neutrophil-depleted wild-type mice were ventilated using clinically relevant ventilator settings (tidal volume 8 ml/kg). The lungs and plasma were collected to determine blood gas values, cytokine profiles and neutrophil influx. RESULTS: Mechanical ventilation resulted in increased pulmonary concentrations of IL-1β and KC and increased pulmonary neutrophil influx compared with non-ventilated mice. Ventilated IL-1αβ knockout mice did not demonstrate this increase in cytokines. No significant differences were observed between wild-type and caspase-1-deficient or pralnacasan-treated mice. In contrast, in anti-KC antibody-treated mice and neutropenic mice, inflammatory parameters decreased in comparison with ventilated non-treated mice. CONCLUSIONS: Our results illustrate that IL-1 is indeed an important cytokine in the inflammatory cascade induced by mechanical ventilation. However, the inflammasome/caspase-1 appears not to be involved in IL-1β processing in this type of inflammatory response. The attenuated inflammatory response observed in ventilated anti-KC-treated and neutropenic mice suggests that IL-1β processing in mechanical ventilation-induced inflammation is mainly mediated by neutrophil factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2197-425X-1-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-47979572016-07-06 IL-1β processing in mechanical ventilation-induced inflammation is dependent on neutrophil factors rather than caspase-1 Timmermans, Kim van der Wal, Selina EI Vaneker, Michiel van der Laak, Jeroen AWM Netea, Mihai G Pickkers, Peter Scheffer, Gert Jan Joosten, Leo AB Kox, Matthijs Intensive Care Med Exp Research PURPOSE: Mechanical ventilation can cause ventilator-induced lung injury, characterized by a sterile inflammatory response in the lungs resulting in tissue damage and respiratory failure. The cytokine interleukin-1β (IL-1β) is thought to play an important role in the pathogenesis of ventilator-induced lung injury. Cleavage of the inactive precursor pro-IL-1β to form bioactive IL-1β is mediated by several types of proteases, of which caspase-1, activated within the inflammasome, is the most important. Herein, we studied the roles of IL-1β, caspase-1 and neutrophil factors in the mechanical ventilation-induced inflammatory response in mice. METHODS: Untreated wild-type mice, IL-1αβ knockout and caspase-1 knockout mice, pralnacasan (a selective caspase-1 inhibitor)-treated mice, anti-keratinocyte-derived chemokine (KC)-treated mice and cyclophosphamide-treated neutrophil-depleted wild-type mice were ventilated using clinically relevant ventilator settings (tidal volume 8 ml/kg). The lungs and plasma were collected to determine blood gas values, cytokine profiles and neutrophil influx. RESULTS: Mechanical ventilation resulted in increased pulmonary concentrations of IL-1β and KC and increased pulmonary neutrophil influx compared with non-ventilated mice. Ventilated IL-1αβ knockout mice did not demonstrate this increase in cytokines. No significant differences were observed between wild-type and caspase-1-deficient or pralnacasan-treated mice. In contrast, in anti-KC antibody-treated mice and neutropenic mice, inflammatory parameters decreased in comparison with ventilated non-treated mice. CONCLUSIONS: Our results illustrate that IL-1 is indeed an important cytokine in the inflammatory cascade induced by mechanical ventilation. However, the inflammasome/caspase-1 appears not to be involved in IL-1β processing in this type of inflammatory response. The attenuated inflammatory response observed in ventilated anti-KC-treated and neutropenic mice suggests that IL-1β processing in mechanical ventilation-induced inflammation is mainly mediated by neutrophil factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2197-425X-1-8) contains supplementary material, which is available to authorized users. Springer International Publishing 2013-10-29 /pmc/articles/PMC4797957/ /pubmed/26266796 http://dx.doi.org/10.1186/2197-425X-1-8 Text en © Timmermans et al.; licensee Springer. 2013 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Timmermans, Kim
van der Wal, Selina EI
Vaneker, Michiel
van der Laak, Jeroen AWM
Netea, Mihai G
Pickkers, Peter
Scheffer, Gert Jan
Joosten, Leo AB
Kox, Matthijs
IL-1β processing in mechanical ventilation-induced inflammation is dependent on neutrophil factors rather than caspase-1
title IL-1β processing in mechanical ventilation-induced inflammation is dependent on neutrophil factors rather than caspase-1
title_full IL-1β processing in mechanical ventilation-induced inflammation is dependent on neutrophil factors rather than caspase-1
title_fullStr IL-1β processing in mechanical ventilation-induced inflammation is dependent on neutrophil factors rather than caspase-1
title_full_unstemmed IL-1β processing in mechanical ventilation-induced inflammation is dependent on neutrophil factors rather than caspase-1
title_short IL-1β processing in mechanical ventilation-induced inflammation is dependent on neutrophil factors rather than caspase-1
title_sort il-1β processing in mechanical ventilation-induced inflammation is dependent on neutrophil factors rather than caspase-1
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797957/
https://www.ncbi.nlm.nih.gov/pubmed/26266796
http://dx.doi.org/10.1186/2197-425X-1-8
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