Kineret®/IL-1ra blocks the IL-1/IL-8 inflammatory cascade during recombinant Panton Valentine Leukocidin-triggered pneumonia but not during S. aureus infection
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...
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creator | Labrousse, Delphine Perret, Magali Hayez, Davy Da Silva, Sonia Badiou, Cédric Couzon, Florence Bes, Michèle Chavanet, Pascal Lina, Gérard Vandenesch, François Croisier-Bertin, Delphine Henry, Thomas |
description | 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.
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.
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.
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. |
doi_str_mv | 10.1371/journal.pone.0097546 |
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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.
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.
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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0097546</identifier><identifier>PMID: 24905099</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activation ; Animals ; Antimicrobial agents ; Bacteria ; Bacterial Toxins - toxicity ; Bacteriology ; Biology and Life Sciences ; Cell activation ; Epithelial cells ; Exotoxins - toxicity ; Hospitals ; Immunology ; In vivo methods and tests ; Infections ; Infectious diseases ; Inflammasomes ; Inflammasomes - drug effects ; Inflammasomes - immunology ; Inflammation ; Interleukin 1 ; Interleukin 1 receptor antagonist ; Interleukin 1 Receptor Antagonist Protein - pharmacology ; Interleukin 1 Receptor Antagonist Protein - therapeutic use ; Interleukin 8 ; Interleukin-1beta - metabolism ; Interleukin-8 - metabolism ; Leukocidin ; Leukocidins - toxicity ; Life Sciences ; Lungs ; Macrophages ; Macrophages - drug effects ; Macrophages - immunology ; Medicine and Health Sciences ; Microbiology and Parasitology ; Neutrophils ; Pneumonia ; Pneumonia, Staphylococcal - drug therapy ; Pneumonia, Staphylococcal - etiology ; Pneumonia, Staphylococcal - metabolism ; Rabbits ; Research and Analysis Methods ; Signaling ; Staphylococcus aureus ; Staphylococcus infections ; Systematic review ; Virology</subject><ispartof>PloS one, 2014-06, Vol.9 (6), p.e97546</ispartof><rights>2014 Labrousse et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2014 Labrousse et al 2014 Labrousse et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c527t-3cf3d4f6bc5a49e8542c9dc4d67c63ac219c10f385439982de827ea0dd21b0cd3</citedby><cites>FETCH-LOGICAL-c527t-3cf3d4f6bc5a49e8542c9dc4d67c63ac219c10f385439982de827ea0dd21b0cd3</cites><orcidid>0000-0002-0687-8565 ; 0000-0001-9412-7106 ; 0000-0002-9236-7998</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048174/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048174/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24905099$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01911490$$DView record in HAL$$Hfree_for_read</backlink></links><search><contributor>Rooijakkers, Suzan H. M.</contributor><creatorcontrib>Labrousse, Delphine</creatorcontrib><creatorcontrib>Perret, Magali</creatorcontrib><creatorcontrib>Hayez, Davy</creatorcontrib><creatorcontrib>Da Silva, Sonia</creatorcontrib><creatorcontrib>Badiou, Cédric</creatorcontrib><creatorcontrib>Couzon, Florence</creatorcontrib><creatorcontrib>Bes, Michèle</creatorcontrib><creatorcontrib>Chavanet, Pascal</creatorcontrib><creatorcontrib>Lina, Gérard</creatorcontrib><creatorcontrib>Vandenesch, François</creatorcontrib><creatorcontrib>Croisier-Bertin, Delphine</creatorcontrib><creatorcontrib>Henry, Thomas</creatorcontrib><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><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.
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.
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.
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.</description><subject>Activation</subject><subject>Animals</subject><subject>Antimicrobial agents</subject><subject>Bacteria</subject><subject>Bacterial Toxins - toxicity</subject><subject>Bacteriology</subject><subject>Biology and Life Sciences</subject><subject>Cell activation</subject><subject>Epithelial cells</subject><subject>Exotoxins - toxicity</subject><subject>Hospitals</subject><subject>Immunology</subject><subject>In vivo methods and tests</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Inflammasomes</subject><subject>Inflammasomes - drug effects</subject><subject>Inflammasomes - immunology</subject><subject>Inflammation</subject><subject>Interleukin 1</subject><subject>Interleukin 1 receptor antagonist</subject><subject>Interleukin 1 Receptor Antagonist Protein - pharmacology</subject><subject>Interleukin 1 Receptor Antagonist Protein - therapeutic use</subject><subject>Interleukin 8</subject><subject>Interleukin-1beta - metabolism</subject><subject>Interleukin-8 - metabolism</subject><subject>Leukocidin</subject><subject>Leukocidins - toxicity</subject><subject>Life Sciences</subject><subject>Lungs</subject><subject>Macrophages</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Medicine and Health Sciences</subject><subject>Microbiology and Parasitology</subject><subject>Neutrophils</subject><subject>Pneumonia</subject><subject>Pneumonia, Staphylococcal - drug therapy</subject><subject>Pneumonia, Staphylococcal - etiology</subject><subject>Pneumonia, Staphylococcal - metabolism</subject><subject>Rabbits</subject><subject>Research and Analysis Methods</subject><subject>Signaling</subject><subject>Staphylococcus 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blocks the IL-1/IL-8 inflammatory cascade during recombinant Panton Valentine Leukocidin-triggered pneumonia but not during S. aureus infection</title><author>Labrousse, Delphine ; Perret, Magali ; Hayez, Davy ; Da Silva, Sonia ; Badiou, Cédric ; Couzon, Florence ; Bes, Michèle ; Chavanet, Pascal ; Lina, Gérard ; Vandenesch, François ; Croisier-Bertin, Delphine ; Henry, Thomas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c527t-3cf3d4f6bc5a49e8542c9dc4d67c63ac219c10f385439982de827ea0dd21b0cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Activation</topic><topic>Animals</topic><topic>Antimicrobial agents</topic><topic>Bacteria</topic><topic>Bacterial Toxins - toxicity</topic><topic>Bacteriology</topic><topic>Biology and Life Sciences</topic><topic>Cell activation</topic><topic>Epithelial cells</topic><topic>Exotoxins - toxicity</topic><topic>Hospitals</topic><topic>Immunology</topic><topic>In vivo methods and tests</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Inflammasomes</topic><topic>Inflammasomes - drug effects</topic><topic>Inflammasomes - immunology</topic><topic>Inflammation</topic><topic>Interleukin 1</topic><topic>Interleukin 1 receptor antagonist</topic><topic>Interleukin 1 Receptor Antagonist Protein - pharmacology</topic><topic>Interleukin 1 Receptor Antagonist Protein - therapeutic use</topic><topic>Interleukin 8</topic><topic>Interleukin-1beta - metabolism</topic><topic>Interleukin-8 - metabolism</topic><topic>Leukocidin</topic><topic>Leukocidins - toxicity</topic><topic>Life Sciences</topic><topic>Lungs</topic><topic>Macrophages</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - immunology</topic><topic>Medicine and Health Sciences</topic><topic>Microbiology and 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Gérard</au><au>Vandenesch, François</au><au>Croisier-Bertin, Delphine</au><au>Henry, Thomas</au><au>Rooijakkers, Suzan H. M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kineret®/IL-1ra blocks the IL-1/IL-8 inflammatory cascade during recombinant Panton Valentine Leukocidin-triggered pneumonia but not during S. aureus infection</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-06-06</date><risdate>2014</risdate><volume>9</volume><issue>6</issue><spage>e97546</spage><pages>e97546-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.
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.
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.
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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24905099</pmid><doi>10.1371/journal.pone.0097546</doi><orcidid>https://orcid.org/0000-0002-0687-8565</orcidid><orcidid>https://orcid.org/0000-0001-9412-7106</orcidid><orcidid>https://orcid.org/0000-0002-9236-7998</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2014-06, Vol.9 (6), p.e97546 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1533745768 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Activation Animals Antimicrobial agents Bacteria Bacterial Toxins - toxicity Bacteriology Biology and Life Sciences Cell activation Epithelial cells Exotoxins - toxicity Hospitals Immunology In vivo methods and tests Infections Infectious diseases Inflammasomes Inflammasomes - drug effects Inflammasomes - immunology Inflammation Interleukin 1 Interleukin 1 receptor antagonist Interleukin 1 Receptor Antagonist Protein - pharmacology Interleukin 1 Receptor Antagonist Protein - therapeutic use Interleukin 8 Interleukin-1beta - metabolism Interleukin-8 - metabolism Leukocidin Leukocidins - toxicity Life Sciences Lungs Macrophages Macrophages - drug effects Macrophages - immunology Medicine and Health Sciences Microbiology and Parasitology Neutrophils Pneumonia Pneumonia, Staphylococcal - drug therapy Pneumonia, Staphylococcal - etiology Pneumonia, Staphylococcal - metabolism Rabbits Research and Analysis Methods Signaling Staphylococcus aureus Staphylococcus infections Systematic review Virology |
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 |
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