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Article: Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus

TitleDelayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus
Authors
KeywordsCelecoxib
Mesalazine
Zanamivir
Issue Date2008
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2008, v. 105 n. 23, p. 8091-8096 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/68078
ISSN
2014 Impact Factor: 9.674
2014 SCImago Journal Rankings: 5.781
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZheng, BJen_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorLin, YPen_HK
dc.contributor.authorZhao, GYen_HK
dc.contributor.authorChan, Cen_HK
dc.contributor.authorZhang, HJen_HK
dc.contributor.authorChen, HLen_HK
dc.contributor.authorWong, SSYen_HK
dc.contributor.authorLau, SKPen_HK
dc.contributor.authorWoo, PCYen_HK
dc.contributor.authorChan, KHen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorYuen, KYen_HK
dc.date.accessioned2010-09-06T06:01:08Z-
dc.date.available2010-09-06T06:01:08Z-
dc.date.issued2008en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2008, v. 105 n. 23, p. 8091-8096en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68078-
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.en_HK
dc.languageengen_HK
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.en_HK
dc.subjectCelecoxiben_HK
dc.subjectMesalazineen_HK
dc.subjectZanamiviren_HK
dc.titleDelayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virusen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0027-8424&volume=105&issue=23&spage=8091&epage=8096.&date=2008&atitle=Delayed+antiviral+plus+immunomodulator+treatment+still+reduces+mortality+in+mice+infected+by+high+inoculum+of+influenza+A/H5N1+virus.en_HK
dc.identifier.emailZheng, BJ:bzheng@hkucc.hku.hken_HK
dc.identifier.emailChan, KW:hrmtckw@hku.hken_HK
dc.identifier.emailChen, HL:hlchen@hkucc.hku.hken_HK
dc.identifier.emailWong, SSY:samsonsy@hkucc.hku.hken_HK
dc.identifier.emailLau, SKP:skplau@hkucc.hku.hken_HK
dc.identifier.emailWoo, PCY:pcywoo@hkucc.hku.hken_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.emailYuen, KY:kyyuen@hkucc.hku.hken_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.identifier.authorityChan, KW=rp00330en_HK
dc.identifier.authorityChen, HL=rp00383en_HK
dc.identifier.authorityWong, SSY=rp00395en_HK
dc.identifier.authorityLau, SKP=rp00486en_HK
dc.identifier.authorityWoo, PCY=rp00430en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityYuen, KY=rp00366en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1073/pnas.0711942105en_HK
dc.identifier.scopuseid_2-s2.0-45849109558en_HK
dc.identifier.hkuros142916en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-45849109558&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume105en_HK
dc.identifier.issue23en_HK
dc.identifier.spage8091en_HK
dc.identifier.epage8096en_HK
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000256781800035-
dc.publisher.placeUnited Statesen_HK
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dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK
dc.identifier.scopusauthoridChan, KW=16444133100en_HK
dc.identifier.scopusauthoridLin, YP=8591935100en_HK
dc.identifier.scopusauthoridZhao, GY=8684553000en_HK
dc.identifier.scopusauthoridChan, C=16021156900en_HK
dc.identifier.scopusauthoridZhang, HJ=24402251800en_HK
dc.identifier.scopusauthoridChen, HL=26643315400en_HK
dc.identifier.scopusauthoridWong, SSY=13310021400en_HK
dc.identifier.scopusauthoridLau, SKP=7401596211en_HK
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dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridYuen, KY=36078079100en_HK

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