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IL-4Rα blockade reduces influenza-associated morbidity in a murine model of allergic asthma

BACKGROUND: Asthma was identified as the most common comorbidity in hospitalized patients during the 2009 H1N1 influenza pandemic. We determined using a murine model of allergic asthma whether these mice experienced increased morbidity from pandemic H1N1 (pH1N1) viral infection and whether blockade...

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Autores principales: Shahangian, Kimia, Ngan, David A., Chen, H. H. Rachel, Oh, Yeni, Tam, Anthony, Wen, Jing, Cheung, Chung, Knight, Darryl A., Dorscheid, Delbert R., Hackett, Tillie L., Hughes, Michael R., McNagny, Kelly M., Hirota, Jeremy A., Niikura, Masahiro, Man, S. F. Paul, Sin, Don D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922715/
https://www.ncbi.nlm.nih.gov/pubmed/33653328
http://dx.doi.org/10.1186/s12931-021-01669-0
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author Shahangian, Kimia
Ngan, David A.
Chen, H. H. Rachel
Oh, Yeni
Tam, Anthony
Wen, Jing
Cheung, Chung
Knight, Darryl A.
Dorscheid, Delbert R.
Hackett, Tillie L.
Hughes, Michael R.
McNagny, Kelly M.
Hirota, Jeremy A.
Niikura, Masahiro
Man, S. F. Paul
Sin, Don D.
author_facet Shahangian, Kimia
Ngan, David A.
Chen, H. H. Rachel
Oh, Yeni
Tam, Anthony
Wen, Jing
Cheung, Chung
Knight, Darryl A.
Dorscheid, Delbert R.
Hackett, Tillie L.
Hughes, Michael R.
McNagny, Kelly M.
Hirota, Jeremy A.
Niikura, Masahiro
Man, S. F. Paul
Sin, Don D.
author_sort Shahangian, Kimia
collection PubMed
description BACKGROUND: Asthma was identified as the most common comorbidity in hospitalized patients during the 2009 H1N1 influenza pandemic. We determined using a murine model of allergic asthma whether these mice experienced increased morbidity from pandemic H1N1 (pH1N1) viral infection and whether blockade of interleukin-4 receptor α (IL-4Rα), a critical mediator of T(h)2 signalling, improved their outcomes. METHODS: Male BALB/c mice were intranasally sensitized with house dust mite antigen (Der p 1) for 2 weeks; the mice were then inoculated intranasally with a single dose of pandemic H1N1 (pH1N1). The mice were administered intraperitoneally anti-IL-4Rα through either a prophylactic or a therapeutic treatment strategy. RESULTS: Infection with pH1N1 of mice sensitized to house dust mite (HDM) led to a 24% loss in weight by day 7 of infection (versus 14% in non-sensitized mice; p < .05). This was accompanied by increased viral load in the airways and a dampened anti-viral host responses to the infection. Treatment of HDM sensitized mice with a monoclonal antibody against IL-4Rα prior to or following pH1N1 infection prevented the excess weight loss, reduced the viral load in the lungs and ameliorated airway eosinophilia and systemic inflammation related to the pH1N1 infection. CONCLUSION: Together, these data implicate allergic asthma as a significant risk factor for H1N1-related morbidity and reveal a potential therapeutic role for IL-4Rα signalling blockade in reducing the severity of influenza infection in those with allergic airway disease.
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spelling pubmed-79227152021-03-02 IL-4Rα blockade reduces influenza-associated morbidity in a murine model of allergic asthma Shahangian, Kimia Ngan, David A. Chen, H. H. Rachel Oh, Yeni Tam, Anthony Wen, Jing Cheung, Chung Knight, Darryl A. Dorscheid, Delbert R. Hackett, Tillie L. Hughes, Michael R. McNagny, Kelly M. Hirota, Jeremy A. Niikura, Masahiro Man, S. F. Paul Sin, Don D. Respir Res Research BACKGROUND: Asthma was identified as the most common comorbidity in hospitalized patients during the 2009 H1N1 influenza pandemic. We determined using a murine model of allergic asthma whether these mice experienced increased morbidity from pandemic H1N1 (pH1N1) viral infection and whether blockade of interleukin-4 receptor α (IL-4Rα), a critical mediator of T(h)2 signalling, improved their outcomes. METHODS: Male BALB/c mice were intranasally sensitized with house dust mite antigen (Der p 1) for 2 weeks; the mice were then inoculated intranasally with a single dose of pandemic H1N1 (pH1N1). The mice were administered intraperitoneally anti-IL-4Rα through either a prophylactic or a therapeutic treatment strategy. RESULTS: Infection with pH1N1 of mice sensitized to house dust mite (HDM) led to a 24% loss in weight by day 7 of infection (versus 14% in non-sensitized mice; p < .05). This was accompanied by increased viral load in the airways and a dampened anti-viral host responses to the infection. Treatment of HDM sensitized mice with a monoclonal antibody against IL-4Rα prior to or following pH1N1 infection prevented the excess weight loss, reduced the viral load in the lungs and ameliorated airway eosinophilia and systemic inflammation related to the pH1N1 infection. CONCLUSION: Together, these data implicate allergic asthma as a significant risk factor for H1N1-related morbidity and reveal a potential therapeutic role for IL-4Rα signalling blockade in reducing the severity of influenza infection in those with allergic airway disease. BioMed Central 2021-03-02 2021 /pmc/articles/PMC7922715/ /pubmed/33653328 http://dx.doi.org/10.1186/s12931-021-01669-0 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Shahangian, Kimia
Ngan, David A.
Chen, H. H. Rachel
Oh, Yeni
Tam, Anthony
Wen, Jing
Cheung, Chung
Knight, Darryl A.
Dorscheid, Delbert R.
Hackett, Tillie L.
Hughes, Michael R.
McNagny, Kelly M.
Hirota, Jeremy A.
Niikura, Masahiro
Man, S. F. Paul
Sin, Don D.
IL-4Rα blockade reduces influenza-associated morbidity in a murine model of allergic asthma
title IL-4Rα blockade reduces influenza-associated morbidity in a murine model of allergic asthma
title_full IL-4Rα blockade reduces influenza-associated morbidity in a murine model of allergic asthma
title_fullStr IL-4Rα blockade reduces influenza-associated morbidity in a murine model of allergic asthma
title_full_unstemmed IL-4Rα blockade reduces influenza-associated morbidity in a murine model of allergic asthma
title_short IL-4Rα blockade reduces influenza-associated morbidity in a murine model of allergic asthma
title_sort il-4rα blockade reduces influenza-associated morbidity in a murine model of allergic asthma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922715/
https://www.ncbi.nlm.nih.gov/pubmed/33653328
http://dx.doi.org/10.1186/s12931-021-01669-0
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