Kineret®/IL-1ra blocks the IL-1/IL-8 inflammatory cascade during recombinant Panton Valentine Leukocidin-triggered pneumonia but not during S. aureus infection.

<h4>Objectives</h4>Community-acquired Staphylococcus aureus necrotizing pneumonia is a life-threatening disease. Panton Valentine Leukocidin (PVL) has been associated with necrotizing pneumonia. PVL triggers inflammasome activation in human macrophages leading to IL-1β release. IL-1β act...

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Autores principales:	Delphine Labrousse, Magali Perret, Davy Hayez, Sonia Da Silva, Cédric Badiou, Florence Couzon, Michèle Bes, Pascal Chavanet, Gérard Lina, François Vandenesch, Delphine Croisier-Bertin, Thomas Henry
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/41b2b06a0a294aa9994639a9b1954651
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spelling	oai:doaj.org-article:41b2b06a0a294aa9994639a9b19546512021-11-18T08:16:42ZKineret®/IL-1ra blocks the IL-1/IL-8 inflammatory cascade during recombinant Panton Valentine Leukocidin-triggered pneumonia but not during S. aureus infection.1932-620310.1371/journal.pone.0097546https://doaj.org/article/41b2b06a0a294aa9994639a9b19546512014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24905099/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objectives</h4>Community-acquired Staphylococcus aureus necrotizing pneumonia is a life-threatening disease. Panton Valentine Leukocidin (PVL) has been associated with necrotizing pneumonia. PVL triggers inflammasome activation in human macrophages leading to IL-1β release. IL-1β activates lung epithelial cells to release IL-8. This study aimed to assess the relevance of this inflammatory cascade in vivo and to test the potential of an IL-1 receptor antagonist (IL-1Ra/Kineret) to decrease inflammation-mediated lung injury.<h4>Methods</h4>We used the sequential instillation of Heat-killed S. aureus and PVL or S. aureus infection to trigger necrotizing pneumonia in rabbits. In these models, we investigated inflammation in the presence or absence of IL-1Ra/Kineret.<h4>Results</h4>We demonstrated that the presence of PVL was associated with IL-1β and IL-8 release in the lung. During PVL-mediated sterile pneumonia, Kineret/IL-1Ra reduced IL-8 production indicating the relevance of the PVL/IL-1/IL-8 cascade in vivo and the potential of Kineret/IL-1Ra to reduce lung inflammation. However, Kineret/IL-1Ra was ineffective in blocking IL-8 production during infection with S. aureus. Furthermore, treatment with Kineret increased the bacterial burden in the lung.<h4>Conclusions</h4>Our data demonstrate PVL-dependent inflammasome activation during S.aureus pneumonia, indicate that IL-1 signaling controls bacterial burden in the lung and suggest that therapy aimed at targeting this pathway might be deleterious during pneumonia.Delphine LabrousseMagali PerretDavy HayezSonia Da SilvaCédric BadiouFlorence CouzonMichèle BesPascal ChavanetGérard LinaFrançois VandeneschDelphine Croisier-BertinThomas HenryPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e97546 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Delphine Labrousse Magali Perret Davy Hayez Sonia Da Silva Cédric Badiou Florence Couzon Michèle Bes Pascal Chavanet Gérard Lina François Vandenesch Delphine Croisier-Bertin Thomas Henry Kineret®/IL-1ra blocks the IL-1/IL-8 inflammatory cascade during recombinant Panton Valentine Leukocidin-triggered pneumonia but not during S. aureus infection.
description	<h4>Objectives</h4>Community-acquired Staphylococcus aureus necrotizing pneumonia is a life-threatening disease. Panton Valentine Leukocidin (PVL) has been associated with necrotizing pneumonia. PVL triggers inflammasome activation in human macrophages leading to IL-1β release. IL-1β activates lung epithelial cells to release IL-8. This study aimed to assess the relevance of this inflammatory cascade in vivo and to test the potential of an IL-1 receptor antagonist (IL-1Ra/Kineret) to decrease inflammation-mediated lung injury.<h4>Methods</h4>We used the sequential instillation of Heat-killed S. aureus and PVL or S. aureus infection to trigger necrotizing pneumonia in rabbits. In these models, we investigated inflammation in the presence or absence of IL-1Ra/Kineret.<h4>Results</h4>We demonstrated that the presence of PVL was associated with IL-1β and IL-8 release in the lung. During PVL-mediated sterile pneumonia, Kineret/IL-1Ra reduced IL-8 production indicating the relevance of the PVL/IL-1/IL-8 cascade in vivo and the potential of Kineret/IL-1Ra to reduce lung inflammation. However, Kineret/IL-1Ra was ineffective in blocking IL-8 production during infection with S. aureus. Furthermore, treatment with Kineret increased the bacterial burden in the lung.<h4>Conclusions</h4>Our data demonstrate PVL-dependent inflammasome activation during S.aureus pneumonia, indicate that IL-1 signaling controls bacterial burden in the lung and suggest that therapy aimed at targeting this pathway might be deleterious during pneumonia.
format	article
author	Delphine Labrousse Magali Perret Davy Hayez Sonia Da Silva Cédric Badiou Florence Couzon Michèle Bes Pascal Chavanet Gérard Lina François Vandenesch Delphine Croisier-Bertin Thomas Henry
author_facet	Delphine Labrousse Magali Perret Davy Hayez Sonia Da Silva Cédric Badiou Florence Couzon Michèle Bes Pascal Chavanet Gérard Lina François Vandenesch Delphine Croisier-Bertin Thomas Henry
author_sort	Delphine Labrousse
title	Kineret®/IL-1ra blocks the IL-1/IL-8 inflammatory cascade during recombinant Panton Valentine Leukocidin-triggered pneumonia but not during S. aureus infection.
title_short	Kineret®/IL-1ra blocks the IL-1/IL-8 inflammatory cascade during recombinant Panton Valentine Leukocidin-triggered pneumonia but not during S. aureus infection.
title_full	Kineret®/IL-1ra blocks the IL-1/IL-8 inflammatory cascade during recombinant Panton Valentine Leukocidin-triggered pneumonia but not during S. aureus infection.
title_fullStr	Kineret®/IL-1ra blocks the IL-1/IL-8 inflammatory cascade during recombinant Panton Valentine Leukocidin-triggered pneumonia but not during S. aureus infection.
title_full_unstemmed	Kineret®/IL-1ra blocks the IL-1/IL-8 inflammatory cascade during recombinant Panton Valentine Leukocidin-triggered pneumonia but not during S. aureus infection.
title_sort	kineret®/il-1ra blocks the il-1/il-8 inflammatory cascade during recombinant panton valentine leukocidin-triggered pneumonia but not during s. aureus infection.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/41b2b06a0a294aa9994639a9b1954651
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Kineret®/IL-1ra blocks the IL-1/IL-8 inflammatory cascade during recombinant Panton Valentine Leukocidin-triggered pneumonia but not during S. aureus infection.

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