Interleukin-6 is a potential biomarker for severe pandemic H1N1 influenza a infection

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

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere38214
JournalPLoS One
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 5 2012

Fingerprint

Biomarkers
Pandemics
pandemic
interleukin-6
influenza
Human Influenza
Interleukin-6
biomarkers
Infection
infection
mice
Fatal Outcome
Critical Care
Mexico
Viral Load
Serum
Inbred C57BL Mouse
Pathology
viral load
lethal genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Paquette, S. G., Banner, D., Zhao, Z., Fang, Y., Huang, S. S. H., León, A. J., ... Kelvin, D. J. (2012). Interleukin-6 is a potential biomarker for severe pandemic H1N1 influenza a infection. PLoS One, 7(6), [e38214]. https://doi.org/10.1371/journal.pone.0038214

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; León, 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.

In: PLoS One, Vol. 7, No. 6, e38214, 05.06.2012.

Research output: Contribution to journalArticle

Paquette, SG, Banner, D, Zhao, Z, Fang, Y, Huang, SSH, León, AJ, Ng, DCK, Almansa, R, Martin-Loeches, I, Ramirez, P, Socias, L, Loza, A, Blanco, J, Sansonetti, P, Rello, J, Andaluz, D, Shum, B, Rubino, S, de Lejarazu, RO, Tran, D, Delogu, G, Fadda, G, Krajden, S, Rubin, BB, Bermejo-Martin, JF, Kelvin, AA & Kelvin, DJ 2012, 'Interleukin-6 is a potential biomarker for severe pandemic H1N1 influenza a infection', PLoS One, vol. 7, no. 6, e38214. https://doi.org/10.1371/journal.pone.0038214
Paquette SG, Banner D, Zhao Z, Fang Y, Huang SSH, León AJ et al. Interleukin-6 is a potential biomarker for severe pandemic H1N1 influenza a infection. PLoS One. 2012 Jun 5;7(6). e38214. https://doi.org/10.1371/journal.pone.0038214
Paquette, Stéphane G. ; Banner, David ; Zhao, Zhen ; Fang, Yuan ; Huang, Stephen S H ; León, 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. In: PLoS One. 2012 ; Vol. 7, No. 6.
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abstract = "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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AU - León, Alberto J.

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AU - Ramirez, Paula

AU - Socias, Lorenzo

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AU - Sansonetti, Paola

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