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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 principales: Paquette, Stéphane G., Banner, David, Zhao, Zhen, Fang, Yuan, Huang, Stephen S. H., Leόn, Alberto J., Ng, Derek C. K., Almansa, Raquel, Martin-Loeches, Ignacio, Ramirez, Paula, Socias, Lorenzo, Loza, Ana, Blanco, Jesus, Sansonetti, Paola, Rello, Jordi, Andaluz, David, Shum, Bianche, Rubino, Salvatore, de Lejarazu, Raul Ortiz, Tran, Dat, Delogu, Giovanni, Fadda, Giovanni, Krajden, Sigmund, Rubin, Barry B., Bermejo-Martin, Jesús F., Kelvin, Alyson A., Kelvin, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367995/
https://www.ncbi.nlm.nih.gov/pubmed/22679491
http://dx.doi.org/10.1371/journal.pone.0038214
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author Paquette, Stéphane G.
Banner, David
Zhao, Zhen
Fang, Yuan
Huang, Stephen S. H.
Leόn, Alberto J.
Ng, Derek C. K.
Almansa, Raquel
Martin-Loeches, Ignacio
Ramirez, Paula
Socias, Lorenzo
Loza, Ana
Blanco, Jesus
Sansonetti, Paola
Rello, Jordi
Andaluz, David
Shum, Bianche
Rubino, Salvatore
de Lejarazu, Raul Ortiz
Tran, Dat
Delogu, Giovanni
Fadda, Giovanni
Krajden, Sigmund
Rubin, Barry B.
Bermejo-Martin, Jesús F.
Kelvin, Alyson A.
Kelvin, David J.
author_facet Paquette, Stéphane G.
Banner, David
Zhao, Zhen
Fang, Yuan
Huang, Stephen S. H.
Leόn, Alberto J.
Ng, Derek C. K.
Almansa, Raquel
Martin-Loeches, Ignacio
Ramirez, Paula
Socias, Lorenzo
Loza, Ana
Blanco, Jesus
Sansonetti, Paola
Rello, Jordi
Andaluz, David
Shum, Bianche
Rubino, Salvatore
de Lejarazu, Raul Ortiz
Tran, Dat
Delogu, Giovanni
Fadda, Giovanni
Krajden, Sigmund
Rubin, Barry B.
Bermejo-Martin, Jesús F.
Kelvin, Alyson A.
Kelvin, David J.
author_sort Paquette, Stéphane G.
collection PubMed
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.
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spelling pubmed-33679952012-06-07 Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection Paquette, Stéphane G. Banner, David Zhao, Zhen Fang, Yuan Huang, Stephen S. H. Leόn, Alberto J. Ng, Derek C. K. Almansa, Raquel Martin-Loeches, Ignacio Ramirez, Paula Socias, Lorenzo Loza, Ana Blanco, Jesus Sansonetti, Paola Rello, Jordi Andaluz, David Shum, Bianche Rubino, Salvatore de Lejarazu, Raul Ortiz Tran, Dat Delogu, Giovanni Fadda, Giovanni Krajden, Sigmund Rubin, Barry B. Bermejo-Martin, Jesús F. Kelvin, Alyson A. Kelvin, David J. PLoS One Research Article 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. Public Library of Science 2012-06-05 /pmc/articles/PMC3367995/ /pubmed/22679491 http://dx.doi.org/10.1371/journal.pone.0038214 Text en Paquette et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Paquette, Stéphane G.
Banner, David
Zhao, Zhen
Fang, Yuan
Huang, Stephen S. H.
Leόn, Alberto J.
Ng, Derek C. K.
Almansa, Raquel
Martin-Loeches, Ignacio
Ramirez, Paula
Socias, Lorenzo
Loza, Ana
Blanco, Jesus
Sansonetti, Paola
Rello, Jordi
Andaluz, David
Shum, Bianche
Rubino, Salvatore
de Lejarazu, Raul Ortiz
Tran, Dat
Delogu, Giovanni
Fadda, Giovanni
Krajden, Sigmund
Rubin, Barry B.
Bermejo-Martin, Jesús F.
Kelvin, Alyson A.
Kelvin, David J.
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
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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367995/
https://www.ncbi.nlm.nih.gov/pubmed/22679491
http://dx.doi.org/10.1371/journal.pone.0038214
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