Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection

Paquette, Stephane G.; Banner, David; Zhao, Zhen; Fang, Yuan; Huang, Stephen S. H.; Leon, Alberto J.; Ng, Derek C. K.; Almansa, Raquel; Martin-Loeches, Ignacio; Ramirez, Paula; Socías, Lorenzo; Loza, Ana; Blanco, Jesus; Sansonetti, Paola; Rello, Jordi; Andaluz-Ojeda, David; Shum, Bianche; Rubino, Salvatore; Ortiz de Lejarazu, Raul; Tran, Dat; Delogu, Giovanni; Fadda, Giovanni; Krajden, Sigmund; Rubin, Barry B.; Bermejo-Martin, Jesus F.; Kelvin, Alyson A.; Kelvin, David J.

Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection

Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cy...

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Autores:	Paquette, Stephane G., Banner, David, Zhao, Zhen, Fang, Yuan, Huang, Stephen S. H., Leon, Alberto J., Ng, Derek C. K., Almansa, Raquel, Martin-Loeches, Ignacio, Ramirez, Paula, Socías, Lorenzo, Loza, Ana, Blanco, Jesus, Sansonetti, Paola, Rello, Jordi, Andaluz-Ojeda, David, Shum, Bianche, Rubino, Salvatore, Ortiz de Lejarazu, Raul, Tran, Dat, Delogu, Giovanni, Fadda, Giovanni, Krajden, Sigmund, Rubin, Barry B., Bermejo-Martin, Jesus F., Kelvin, Alyson A., Kelvin, David J.
Tipo de recurso:	artículo
Fecha de publicación:	2012
País:	España
Institución:	Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:	Docusalut
Idioma:	inglés
OAI Identifier:	oai:docusalut.com:20.500.13003/16625
Acceso en línea:	https://hdl.handle.net/20.500.13003/16625
Access Level:	acceso abierto
Palabra clave:	Mice Pandemics Viral Load Biomarkers Mice, Inbred BALB C Female Animals Interleukin-6 Mice, Inbred C57BL Orthomyxoviridae Infections Influenza A Virus, H1N1 Subtype Carga Viral Pandemias Ratones Endogámicos BALB C Subtipo H1N1 del Virus de la Influenza A Animales Interleucina-6 Ratones Femenino Infecciones por Orthomyxoviridae Ratones Endogámicos C57BL Biomarcadores

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spelling	Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A InfectionPaquette, Stephane G.Banner, DavidZhao, ZhenFang, YuanHuang, Stephen S. H.Leon, Alberto J.Ng, Derek C. K.Almansa, RaquelMartin-Loeches, IgnacioRamirez, PaulaSocías, LorenzoLoza, AnaBlanco, JesusSansonetti, PaolaRello, JordiAndaluz-Ojeda, DavidShum, BiancheRubino, SalvatoreOrtiz de Lejarazu, RaulTran, DatDelogu, GiovanniFadda, GiovanniKrajden, SigmundRubin, Barry B.Bermejo-Martin, Jesus F.Kelvin, Alyson A.Kelvin, David J.MicePandemicsViral LoadBiomarkersMice, Inbred BALB CFemaleAnimalsInterleukin-6Mice, Inbred C57BLOrthomyxoviridae InfectionsInfluenza A Virus, H1N1 SubtypeCarga ViralPandemiasRatones Endogámicos BALB CSubtipo H1N1 del Virus de la Influenza AAnimalesInterleucina-6RatonesFemeninoInfecciones por OrthomyxoviridaeRatones Endogámicos C57BLBiomarcadoresPandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data.Public Library Science20122012-06-0520122012-06-05research articlehttp://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.13003/16625reponame:Docusalutinstname:Conselleria de Salut i Consum del Govern de les Illes BalearsInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 3.0 Unportedhttps://creativecommons.org/licenses/by/3.0/info:eu-repo/semantics/openAccessoai:docusalut.com:20.500.13003/166252026-06-22T12:44:07Z
dc.title.none.fl_str_mv	Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection
title	Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection
spellingShingle	Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection Paquette, Stephane G. Mice Pandemics Viral Load Biomarkers Mice, Inbred BALB C Female Animals Interleukin-6 Mice, Inbred C57BL Orthomyxoviridae Infections Influenza A Virus, H1N1 Subtype Carga Viral Pandemias Ratones Endogámicos BALB C Subtipo H1N1 del Virus de la Influenza A Animales Interleucina-6 Ratones Femenino Infecciones por Orthomyxoviridae Ratones Endogámicos C57BL Biomarcadores
title_short	Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection
title_full	Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection
title_fullStr	Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection
title_full_unstemmed	Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection
title_sort	Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection
dc.creator.none.fl_str_mv	Paquette, Stephane G. Banner, David Zhao, Zhen Fang, Yuan Huang, Stephen S. H. Leon, Alberto J. Ng, Derek C. K. Almansa, Raquel Martin-Loeches, Ignacio Ramirez, Paula Socías, Lorenzo Loza, Ana Blanco, Jesus Sansonetti, Paola Rello, Jordi Andaluz-Ojeda, David Shum, Bianche Rubino, Salvatore Ortiz de Lejarazu, Raul Tran, Dat Delogu, Giovanni Fadda, Giovanni Krajden, Sigmund Rubin, Barry B. Bermejo-Martin, Jesus F. Kelvin, Alyson A. Kelvin, David J.
author	Paquette, Stephane G.
author_facet	Paquette, Stephane G. Banner, David Zhao, Zhen Fang, Yuan Huang, Stephen S. H. Leon, Alberto J. Ng, Derek C. K. Almansa, Raquel Martin-Loeches, Ignacio Ramirez, Paula Socías, Lorenzo Loza, Ana Blanco, Jesus Sansonetti, Paola Rello, Jordi Andaluz-Ojeda, David Shum, Bianche Rubino, Salvatore Ortiz de Lejarazu, Raul Tran, Dat Delogu, Giovanni Fadda, Giovanni Krajden, Sigmund Rubin, Barry B. Bermejo-Martin, Jesus F. Kelvin, Alyson A. Kelvin, David J.
author_role	author
author2	Banner, David Zhao, Zhen Fang, Yuan Huang, Stephen S. H. Leon, Alberto J. Ng, Derek C. K. Almansa, Raquel Martin-Loeches, Ignacio Ramirez, Paula Socías, Lorenzo Loza, Ana Blanco, Jesus Sansonetti, Paola Rello, Jordi Andaluz-Ojeda, David Shum, Bianche Rubino, Salvatore Ortiz de Lejarazu, Raul Tran, Dat Delogu, Giovanni Fadda, Giovanni Krajden, Sigmund Rubin, Barry B. Bermejo-Martin, Jesus F. Kelvin, Alyson A. Kelvin, David J.
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv	Mice Pandemics Viral Load Biomarkers Mice, Inbred BALB C Female Animals Interleukin-6 Mice, Inbred C57BL Orthomyxoviridae Infections Influenza A Virus, H1N1 Subtype Carga Viral Pandemias Ratones Endogámicos BALB C Subtipo H1N1 del Virus de la Influenza A Animales Interleucina-6 Ratones Femenino Infecciones por Orthomyxoviridae Ratones Endogámicos C57BL Biomarcadores
topic	Mice Pandemics Viral Load Biomarkers Mice, Inbred BALB C Female Animals Interleukin-6 Mice, Inbred C57BL Orthomyxoviridae Infections Influenza A Virus, H1N1 Subtype Carga Viral Pandemias Ratones Endogámicos BALB C Subtipo H1N1 del Virus de la Influenza A Animales Interleucina-6 Ratones Femenino Infecciones por Orthomyxoviridae Ratones Endogámicos C57BL Biomarcadores
description	Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data.
publishDate	2012
dc.date.none.fl_str_mv	2012 2012-06-05 2012 2012-06-05
dc.type.none.fl_str_mv	research article http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/20.500.13003/16625
url	https://hdl.handle.net/20.500.13003/16625
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 3.0 Unported https://creativecommons.org/licenses/by/3.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 3.0 Unported https://creativecommons.org/licenses/by/3.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Public Library Science
publisher.none.fl_str_mv	Public Library Science
dc.source.none.fl_str_mv	reponame:Docusalut instname:Conselleria de Salut i Consum del Govern de les Illes Balears
instname_str	Conselleria de Salut i Consum del Govern de les Illes Balears
reponame_str	Docusalut
collection	Docusalut
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection

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