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Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza
BACKGROUND: Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. Th...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175217/ https://www.ncbi.nlm.nih.gov/pubmed/21880131 http://dx.doi.org/10.1186/1471-2334-11-232 |
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author | Almansa, Raquel Anton, Andres Ramirez, Paula Martin-Loeches, Ignacio Banner, David Pumarola, Tomás Xu, Luoling Blanco, Jesús Ran, Longsi Lopez-Campos, Guillermo Martin-Sanchez, Fernando Socias, Lorenzo Loza, Ana Andaluz, David Maravi, Enrique Gordón, Mónica Gallegos, Maria C Fernandez, Victoria León, Cristobal Merino, Pedro Marcos, Maria Ángeles Gandía, Francisco Bobillo, Felipe Resino, Salvador Eiros, Jose Mª Castro, Carmen Mateo, Paula Gonzalez-Rivera, Milagros Rello, Jordi de Lejarazu, Raul Ortiz Kelvin, David J Bermejo-Martin, Jesus F |
author_facet | Almansa, Raquel Anton, Andres Ramirez, Paula Martin-Loeches, Ignacio Banner, David Pumarola, Tomás Xu, Luoling Blanco, Jesús Ran, Longsi Lopez-Campos, Guillermo Martin-Sanchez, Fernando Socias, Lorenzo Loza, Ana Andaluz, David Maravi, Enrique Gordón, Mónica Gallegos, Maria C Fernandez, Victoria León, Cristobal Merino, Pedro Marcos, Maria Ángeles Gandía, Francisco Bobillo, Felipe Resino, Salvador Eiros, Jose Mª Castro, Carmen Mateo, Paula Gonzalez-Rivera, Milagros Rello, Jordi de Lejarazu, Raul Ortiz Kelvin, David J Bermejo-Martin, Jesus F |
author_sort | Almansa, Raquel |
collection | PubMed |
description | BACKGROUND: Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients. METHODS: Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient. RESULTS: Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-γ, the chemotactic factors MIP-1β, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p < 0.05). Correlation studies demonstrated also the existence of a significant positive association between the levels of these mediators, evidencing that they are simultaneously regulated in response to the virus. CONCLUSIONS: Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1. |
format | Online Article Text |
id | pubmed-3175217 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-31752172011-09-18 Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza Almansa, Raquel Anton, Andres Ramirez, Paula Martin-Loeches, Ignacio Banner, David Pumarola, Tomás Xu, Luoling Blanco, Jesús Ran, Longsi Lopez-Campos, Guillermo Martin-Sanchez, Fernando Socias, Lorenzo Loza, Ana Andaluz, David Maravi, Enrique Gordón, Mónica Gallegos, Maria C Fernandez, Victoria León, Cristobal Merino, Pedro Marcos, Maria Ángeles Gandía, Francisco Bobillo, Felipe Resino, Salvador Eiros, Jose Mª Castro, Carmen Mateo, Paula Gonzalez-Rivera, Milagros Rello, Jordi de Lejarazu, Raul Ortiz Kelvin, David J Bermejo-Martin, Jesus F BMC Infect Dis Research Article BACKGROUND: Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients. METHODS: Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient. RESULTS: Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-γ, the chemotactic factors MIP-1β, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p < 0.05). Correlation studies demonstrated also the existence of a significant positive association between the levels of these mediators, evidencing that they are simultaneously regulated in response to the virus. CONCLUSIONS: Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1. BioMed Central 2011-08-31 /pmc/articles/PMC3175217/ /pubmed/21880131 http://dx.doi.org/10.1186/1471-2334-11-232 Text en Copyright ©2011 Almansa et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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 Article Almansa, Raquel Anton, Andres Ramirez, Paula Martin-Loeches, Ignacio Banner, David Pumarola, Tomás Xu, Luoling Blanco, Jesús Ran, Longsi Lopez-Campos, Guillermo Martin-Sanchez, Fernando Socias, Lorenzo Loza, Ana Andaluz, David Maravi, Enrique Gordón, Mónica Gallegos, Maria C Fernandez, Victoria León, Cristobal Merino, Pedro Marcos, Maria Ángeles Gandía, Francisco Bobillo, Felipe Resino, Salvador Eiros, Jose Mª Castro, Carmen Mateo, Paula Gonzalez-Rivera, Milagros Rello, Jordi de Lejarazu, Raul Ortiz Kelvin, David J Bermejo-Martin, Jesus F Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza |
title | Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza |
title_full | Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza |
title_fullStr | Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza |
title_full_unstemmed | Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza |
title_short | Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza |
title_sort | direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175217/ https://www.ncbi.nlm.nih.gov/pubmed/21880131 http://dx.doi.org/10.1186/1471-2334-11-232 |
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