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Article: Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus
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TitleDelayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus
 
AuthorsZheng, BJ1
Chan, KW1
Lin, YP1
Zhao, GY1
Chan, C1
Zhang, HJ1
Chen, HL1
Wong, SSY1
Lau, SKP1
Woo, PCY1
Chan, KH1
Jin, DY1
Yuen, KY1
 
KeywordsCelecoxib
Mesalazine
Zanamivir
 
Issue Date2008
 
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
 
CitationProceedings Of The National Academy Of Sciences Of The United States Of America, 2008, v. 105 n. 23, p. 8091-8096 [How to Cite?]
DOI: http://dx.doi.org/10.1073/pnas.0711942105
 
AbstractThe mortality of human infection by influenza A/H5N1 virus can exceed 80%. The high mortality and its poor response to the neuraminidase inhibitor oseltamivir have been attributed to uncontrolled virus-induced cytokine storm. We challenged BALB/c mice with 1,000 LD50 of influenza A/Vietnam/1194/04. Survival, body weight, histopathology, inflammatory markers, viral loads, T lymphocyte counts, and neutralizing antibody response were documented in infected mice treated individually or in combination with zanamvir, celecoxib, gemfibrozil, and mesalazine. To imitate the real-life scenario, treatment was initiated at 48 h after viral challenge. There were significant improvements in survival rate (P = 0.02), survival time (P < 0.02), and inflammatory markers (P < 0.01) in the group treated with a triple combination of zanamivir, celecoxib, and mesalazine when compared with zanamivir alone. Zanamivir with or without immunomodulators reduced viral load to a similar extent. Insignificant prolongation of survival was observed when individual agents were used alone. Significantly higher levels of CD4 + and CD8 + T lymphocytes and less pulmonary inflammation were also found in the group receiving triple therapy. Zanamivir alone reduced viral load but not inflammation and mortality. The survival benefits of adding celecoxib and mesalazine to zanamivir could be caused by their synergistic effects in reducing cytokine dysfunction and preventing apoptosis. Combinations of a neuraminidase inhibitor with these immunomodulators should be considered in randomized controlled treatment trials of patients suffering from H5N1 infection. © 2008 by The National Academy of Sciences of the USA.
 
ISSN0027-8424
2012 Impact Factor: 9.737
2012 SCImago Journal Rankings: 5.473
 
DOIhttp://dx.doi.org/10.1073/pnas.0711942105
 
ISI Accession Number IDWOS:000256781800035
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorZheng, BJ
 
dc.contributor.authorChan, KW
 
dc.contributor.authorLin, YP
 
dc.contributor.authorZhao, GY
 
dc.contributor.authorChan, C
 
dc.contributor.authorZhang, HJ
 
dc.contributor.authorChen, HL
 
dc.contributor.authorWong, SSY
 
dc.contributor.authorLau, SKP
 
dc.contributor.authorWoo, PCY
 
dc.contributor.authorChan, KH
 
dc.contributor.authorJin, DY
 
dc.contributor.authorYuen, KY
 
dc.date.accessioned2010-09-06T06:01:08Z
 
dc.date.available2010-09-06T06:01:08Z
 
dc.date.issued2008
 
dc.description.abstractThe mortality of human infection by influenza A/H5N1 virus can exceed 80%. The high mortality and its poor response to the neuraminidase inhibitor oseltamivir have been attributed to uncontrolled virus-induced cytokine storm. We challenged BALB/c mice with 1,000 LD50 of influenza A/Vietnam/1194/04. Survival, body weight, histopathology, inflammatory markers, viral loads, T lymphocyte counts, and neutralizing antibody response were documented in infected mice treated individually or in combination with zanamvir, celecoxib, gemfibrozil, and mesalazine. To imitate the real-life scenario, treatment was initiated at 48 h after viral challenge. There were significant improvements in survival rate (P = 0.02), survival time (P < 0.02), and inflammatory markers (P < 0.01) in the group treated with a triple combination of zanamivir, celecoxib, and mesalazine when compared with zanamivir alone. Zanamivir with or without immunomodulators reduced viral load to a similar extent. Insignificant prolongation of survival was observed when individual agents were used alone. Significantly higher levels of CD4 + and CD8 + T lymphocytes and less pulmonary inflammation were also found in the group receiving triple therapy. Zanamivir alone reduced viral load but not inflammation and mortality. The survival benefits of adding celecoxib and mesalazine to zanamivir could be caused by their synergistic effects in reducing cytokine dysfunction and preventing apoptosis. Combinations of a neuraminidase inhibitor with these immunomodulators should be considered in randomized controlled treatment trials of patients suffering from H5N1 infection. © 2008 by The National Academy of Sciences of the USA.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2008, v. 105 n. 23, p. 8091-8096 [How to Cite?]
DOI: http://dx.doi.org/10.1073/pnas.0711942105
 
dc.identifier.doihttp://dx.doi.org/10.1073/pnas.0711942105
 
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dc.identifier.isiWOS:000256781800035
 
dc.identifier.issn0027-8424
2012 Impact Factor: 9.737
2012 SCImago Journal Rankings: 5.473
 
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dc.identifier.urihttp://hdl.handle.net/10722/68078
 
dc.identifier.volume105
 
dc.languageeng
 
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
 
dc.publisher.placeUnited States
 
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America
 
dc.relation.referencesReferences in Scopus
 
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.
 
dc.subjectCelecoxib
 
dc.subjectMesalazine
 
dc.subjectZanamivir
 
dc.titleDelayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong