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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Detalhes bibliográficos
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 documento: artigo
Data de publicação:2012
País:España
Recursos:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositório:Docusalut
Idioma:inglês
OAI Identifier:oai:docusalut.com:20.500.13003/16625
Acesso em linha:https://hdl.handle.net/20.500.13003/16625
Access Level:Acceso aberto
Palavra-chave: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
Descrição
Resumo: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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