Rapamycin adjuvant and exacerbation of severe influenza in an experimental mouse model

Abstract Influenza virus infection often causes severe disease and acute respiratory distress syndrome. It is a common belief that overwhelming immune response contributes to the severe illness. Physicians and researchers have put forth immune modulation as salvage therapy for better recovery. Howev...

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Autores principales:	Ching-Tai Huang, Chen-Yiu Hung, Tse-Ching Chen, Chun-Yen Lin, Yung-Chang Lin, Chia-Shiang Chang, Yueh-Chia He, Yu-Lin Huang, Avijit Dutta
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c3b98c07eaed411a853d4e99c424f041
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spelling	oai:doaj.org-article:c3b98c07eaed411a853d4e99c424f0412021-12-02T12:32:50ZRapamycin adjuvant and exacerbation of severe influenza in an experimental mouse model10.1038/s41598-017-04365-62045-2322https://doaj.org/article/c3b98c07eaed411a853d4e99c424f0412017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04365-6https://doaj.org/toc/2045-2322Abstract Influenza virus infection often causes severe disease and acute respiratory distress syndrome. It is a common belief that overwhelming immune response contributes to the severe illness. Physicians and researchers have put forth immune modulation as salvage therapy for better recovery. However, empiric corticosteroid failed in both humans and animal models. Reported success with Rapamycin in humans prompted a comprehensive animal study and mechanistic dissection. Here we report the effect of Rapamycin alone or in combination with Oseltamivir for severe influenza in BALB/c mice. We found that Rapamycin had no antiviral effect against H1N1, H3N2 and novel-H1N1 influenza viruses in vitro. Rapamycin alone aggravated the severe disease of PR8 H1N1 influenza virus infection in mice. Timely Oseltamivir anti-viral therapy abolished the disease. Delayed Oseltamivir treatment could not prevent severe illness and Rapamycin adjuvant was associated with exacerbated disease. Rapamycin adjuvant suppressed influenza hemagglutinin antigen-specific T cell immunity and impaired virus clearance from the lungs. It also resulted in intensified lung pathology with increased intra-alveolar edema and hyaline deposition. Rapamycin may work as the salvage therapy for severe influenza but it is very difficult to define the appropriate window for such treatment to take effect.Ching-Tai HuangChen-Yiu HungTse-Ching ChenChun-Yen LinYung-Chang LinChia-Shiang ChangYueh-Chia HeYu-Lin HuangAvijit DuttaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ching-Tai Huang Chen-Yiu Hung Tse-Ching Chen Chun-Yen Lin Yung-Chang Lin Chia-Shiang Chang Yueh-Chia He Yu-Lin Huang Avijit Dutta Rapamycin adjuvant and exacerbation of severe influenza in an experimental mouse model
description	Abstract Influenza virus infection often causes severe disease and acute respiratory distress syndrome. It is a common belief that overwhelming immune response contributes to the severe illness. Physicians and researchers have put forth immune modulation as salvage therapy for better recovery. However, empiric corticosteroid failed in both humans and animal models. Reported success with Rapamycin in humans prompted a comprehensive animal study and mechanistic dissection. Here we report the effect of Rapamycin alone or in combination with Oseltamivir for severe influenza in BALB/c mice. We found that Rapamycin had no antiviral effect against H1N1, H3N2 and novel-H1N1 influenza viruses in vitro. Rapamycin alone aggravated the severe disease of PR8 H1N1 influenza virus infection in mice. Timely Oseltamivir anti-viral therapy abolished the disease. Delayed Oseltamivir treatment could not prevent severe illness and Rapamycin adjuvant was associated with exacerbated disease. Rapamycin adjuvant suppressed influenza hemagglutinin antigen-specific T cell immunity and impaired virus clearance from the lungs. It also resulted in intensified lung pathology with increased intra-alveolar edema and hyaline deposition. Rapamycin may work as the salvage therapy for severe influenza but it is very difficult to define the appropriate window for such treatment to take effect.
format	article
author	Ching-Tai Huang Chen-Yiu Hung Tse-Ching Chen Chun-Yen Lin Yung-Chang Lin Chia-Shiang Chang Yueh-Chia He Yu-Lin Huang Avijit Dutta
author_facet	Ching-Tai Huang Chen-Yiu Hung Tse-Ching Chen Chun-Yen Lin Yung-Chang Lin Chia-Shiang Chang Yueh-Chia He Yu-Lin Huang Avijit Dutta
author_sort	Ching-Tai Huang
title	Rapamycin adjuvant and exacerbation of severe influenza in an experimental mouse model
title_short	Rapamycin adjuvant and exacerbation of severe influenza in an experimental mouse model
title_full	Rapamycin adjuvant and exacerbation of severe influenza in an experimental mouse model
title_fullStr	Rapamycin adjuvant and exacerbation of severe influenza in an experimental mouse model
title_full_unstemmed	Rapamycin adjuvant and exacerbation of severe influenza in an experimental mouse model
title_sort	rapamycin adjuvant and exacerbation of severe influenza in an experimental mouse model
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c3b98c07eaed411a853d4e99c424f041
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Rapamycin adjuvant and exacerbation of severe influenza in an experimental mouse model

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