Increased Survival after Gemfibrozil Treatment of Severe Mouse Influenza▿
Identifieur interne : 000263 ( Pmc/Curation ); précédent : 000262; suivant : 000264Increased Survival after Gemfibrozil Treatment of Severe Mouse Influenza▿
Auteurs : Alison Budd ; Lisa Alleva ; Mohammed Alsharifi ; Aulikki Koskinen ; Victoria Smythe ; Arno Müllbacher ; Jeff Wood ; Ian ClarkSource :
- Antimicrobial Agents and Chemotherapy [ 0066-4804 ] ; 2007.
Abstract
Gemfibrozil, an agent that inhibits production of proinflammatory cytokines in addition to its clinically useful lipid-lowering activity, increased survival in BALB/c mice that were already ill from infection by influenza virus A/Japan/305/57 (H2N2). Gemfibrozil was administered intraperitoneally once daily from days 4 to 10 after intranasal exposure to the virus. Survival increased from 26% in vehicle-treated mice (
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DOI: 10.1128/AAC.00219-07
PubMed: 17562808
PubMed Central: 1932503
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Increased Survival after Gemfibrozil Treatment of Severe Mouse Influenza<xref ref-type="fn" rid="fn2">▿</xref> </title><author><name sortKey="Budd, Alison" sort="Budd, Alison" uniqKey="Budd A" first="Alison" last="Budd">Alison Budd</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Alleva, Lisa" sort="Alleva, Lisa" uniqKey="Alleva L" first="Lisa" last="Alleva">Lisa Alleva</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Alsharifi, Mohammed" sort="Alsharifi, Mohammed" uniqKey="Alsharifi M" first="Mohammed" last="Alsharifi">Mohammed Alsharifi</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Koskinen, Aulikki" sort="Koskinen, Aulikki" uniqKey="Koskinen A" first="Aulikki" last="Koskinen">Aulikki Koskinen</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Smythe, Victoria" sort="Smythe, Victoria" uniqKey="Smythe V" first="Victoria" last="Smythe">Victoria Smythe</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Mullbacher, Arno" sort="Mullbacher, Arno" uniqKey="Mullbacher A" first="Arno" last="Müllbacher">Arno Müllbacher</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Wood, Jeff" sort="Wood, Jeff" uniqKey="Wood J" first="Jeff" last="Wood">Jeff Wood</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Clark, Ian" sort="Clark, Ian" uniqKey="Clark I" first="Ian" last="Clark">Ian Clark</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">17562808</idno><idno type="pmc">1932503</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1932503</idno><idno type="RBID">PMC:1932503</idno><idno type="doi">10.1128/AAC.00219-07</idno><date when="2007">2007</date><idno type="wicri:Area/Pmc/Corpus">000263</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000263</idno><idno type="wicri:Area/Pmc/Curation">000263</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000263</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Increased Survival after Gemfibrozil Treatment of Severe Mouse Influenza<xref ref-type="fn" rid="fn2">▿</xref> </title><author><name sortKey="Budd, Alison" sort="Budd, Alison" uniqKey="Budd A" first="Alison" last="Budd">Alison Budd</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Alleva, Lisa" sort="Alleva, Lisa" uniqKey="Alleva L" first="Lisa" last="Alleva">Lisa Alleva</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Alsharifi, Mohammed" sort="Alsharifi, Mohammed" uniqKey="Alsharifi M" first="Mohammed" last="Alsharifi">Mohammed Alsharifi</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Koskinen, Aulikki" sort="Koskinen, Aulikki" uniqKey="Koskinen A" first="Aulikki" last="Koskinen">Aulikki Koskinen</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Smythe, Victoria" sort="Smythe, Victoria" uniqKey="Smythe V" first="Victoria" last="Smythe">Victoria Smythe</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Mullbacher, Arno" sort="Mullbacher, Arno" uniqKey="Mullbacher A" first="Arno" last="Müllbacher">Arno Müllbacher</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Wood, Jeff" sort="Wood, Jeff" uniqKey="Wood J" first="Jeff" last="Wood">Jeff Wood</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Clark, Ian" sort="Clark, Ian" uniqKey="Clark I" first="Ian" last="Clark">Ian Clark</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Antimicrobial Agents and Chemotherapy</title><idno type="ISSN">0066-4804</idno><idno type="eISSN">1098-6596</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Gemfibrozil, an agent that inhibits production of proinflammatory cytokines in addition to its clinically useful lipid-lowering activity, increased survival in BALB/c mice that were already ill from infection by influenza virus A/Japan/305/57 (H2N2). Gemfibrozil was administered intraperitoneally once daily from days 4 to 10 after intranasal exposure to the virus. Survival increased from 26% in vehicle-treated mice (<italic>n</italic> = 50) to 52% in mice given gemfibrozil at 60 mg/kg/day (<italic>n</italic> = 46) (<italic>P</italic> = 0.0026). If this principle translates to patients, a drug already approved for human use, albeit by a different route for another purpose, might be adapted relatively fast for use against influenza, conceivably including human infection with a derivative of the avian H5N1 strain.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Antimicrob Agents Chemother</journal-id><journal-id journal-id-type="publisher-id">aac</journal-id><journal-title>Antimicrobial Agents and Chemotherapy</journal-title><issn pub-type="ppub">0066-4804</issn><issn pub-type="epub">1098-6596</issn><publisher><publisher-name>American Society for Microbiology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">17562808</article-id><article-id pub-id-type="pmc">1932503</article-id><article-id pub-id-type="publisher-id">0219-07</article-id><article-id pub-id-type="doi">10.1128/AAC.00219-07</article-id><article-categories><subj-group subj-group-type="heading"><subject>Antiviral Agents</subject></subj-group></article-categories><title-group><article-title>Increased Survival after Gemfibrozil Treatment of Severe Mouse Influenza<xref ref-type="fn" rid="fn2">▿</xref> </article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Budd</surname><given-names>Alison</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="fn" rid="fn1">†</xref></contrib><contrib contrib-type="author"><name><surname>Alleva</surname><given-names>Lisa</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="fn" rid="fn1">†</xref></contrib><contrib contrib-type="author"><name><surname>Alsharifi</surname><given-names>Mohammed</given-names></name><xref ref-type="aff" rid="aff1">2</xref></contrib><contrib contrib-type="author"><name><surname>Koskinen</surname><given-names>Aulikki</given-names></name><xref ref-type="aff" rid="aff1">2</xref></contrib><contrib contrib-type="author"><name><surname>Smythe</surname><given-names>Victoria</given-names></name><xref ref-type="aff" rid="aff1">2</xref></contrib><contrib contrib-type="author"><name><surname>Müllbacher</surname><given-names>Arno</given-names></name><xref ref-type="aff" rid="aff1">2</xref></contrib><contrib contrib-type="author"><name><surname>Wood</surname><given-names>Jeff</given-names></name><xref ref-type="aff" rid="aff1">3</xref></contrib><contrib contrib-type="author"><name><surname>Clark</surname><given-names>Ian</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="aff1">School of Biochemistry and Molecular Biology,<label>1</label> John Curtin School of Medical Research,<label>2</label> Statistical Consulting Unit, Australian National University, Canberra ACT 0200, Australia<label>3</label></aff><author-notes><fn id="cor1"><label>*</label><p>Corresponding author. Mailing address: School of Biochemistry and Molecular Biology, Australian National University, Canberra ACT 0200, Australia. Phone: 61.2.6125.4363. Fax: 61.2.6125.0313. E-mail: <email>ian.clark@anu.edu.au</email></p></fn><fn id="fn1"><label>†</label><p>A.B. and L.A. contributed equally to this study.</p></fn></author-notes><pub-date pub-type="ppub"><month>8</month><year>2007</year></pub-date><pub-date pub-type="epub"><day>11</day><month>6</month><year>2007</year></pub-date><volume>51</volume><issue>8</issue><fpage>2965</fpage><lpage>2968</lpage><history><date date-type="received"><day>13</day><month>2</month><year>2007</year></date><date date-type="rev-recd"><day>29</day><month>3</month><year>2007</year></date><date date-type="accepted"><day>24</day><month>5</month><year>2007</year></date></history><copyright-statement>Copyright © 2007, American Society for Microbiology</copyright-statement><copyright-year>2007</copyright-year><self-uri xlink:title="pdf" xlink:href="zac00807002965.pdf"></self-uri><abstract><p>Gemfibrozil, an agent that inhibits production of proinflammatory cytokines in addition to its clinically useful lipid-lowering activity, increased survival in BALB/c mice that were already ill from infection by influenza virus A/Japan/305/57 (H2N2). Gemfibrozil was administered intraperitoneally once daily from days 4 to 10 after intranasal exposure to the virus. Survival increased from 26% in vehicle-treated mice (<italic>n</italic> = 50) to 52% in mice given gemfibrozil at 60 mg/kg/day (<italic>n</italic> = 46) (<italic>P</italic> = 0.0026). If this principle translates to patients, a drug already approved for human use, albeit by a different route for another purpose, might be adapted relatively fast for use against influenza, conceivably including human infection with a derivative of the avian H5N1 strain.</p></abstract></article-meta></front><floats-wrap><fig position="float" id="f1"><label>FIG. 1.</label><caption><p>Effect of gemfibrozil on survival of BALB/c mice with severe influenza. Mice were infected with influenza virus A/Japan/305/57 and treated with vehicle or 20 mg/kg, 40 mg/kg, or 60 mg/kg gemfibrozil once daily from days 4 to 10 after virus exposure. These results are from a single experiment (vehicle, <italic>n</italic> = 9; 20 mg/kg, <italic>n</italic> = 10; 40 mg/kg, <italic>n</italic> = 9; 60 mg/kg, <italic>n</italic> = 10).</p></caption><graphic xlink:href="zac0080766910001"></graphic></fig><fig position="float" id="f2"><label>FIG. 2.</label><caption><p>Effect of 60 mg/kg gemfibrozil on survival of BALB/c mice with severe influenza. Mice were infected with influenza virus A/Japan/305/57 and treated with vehicle or 60 mg/kg gemfibrozil once daily from days 4 to 10 after virus exposure. These results are pooled from four separate experiments (vehicle, <italic>n</italic> = 50; gemfibrozil, <italic>n</italic> = 46). Statistical analysis using the log rank test determined the increase in survival time with gemfibrozil treatment to be significant (<italic>P</italic> = 0.0026).</p></caption><graphic xlink:href="zac0080766910002"></graphic></fig><fig position="float" id="f3"><label>FIG. 3.</label><caption><p>Effect of 60 mg/kg gemfibrozil on survival of BALB/c mice with severe systemic inflammation. Mice were given 30 mg/kg LPS (<italic>E. coli</italic> serotype O111:B4) and treated with a single dose of vehicle or 60 mg/kg gemfibrozil either 1 h before or 2 h after LPS injection. These results are from a single experiment; <italic>n</italic> = 20 for each group. Statistical analysis using the log rank test determined that a single dose of 60 mg/kg gemfibrozil 1 h before LPS significantly increased survival (<italic>P</italic> < 0.001).</p></caption><graphic xlink:href="zac0080766910003"></graphic></fig><table-wrap position="float" id="t1"><label>TABLE 1.</label><caption><p>Weight loss in mice infected with influenza virus (A/Japan/305/57) given gemfibrozil once daily from days 4 to 10 after virus exposure</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="2" align="center" valign="middle">Gemfibrozil dose (mg/kg/day)</th><th colspan="1" rowspan="2" align="center" valign="middle">No. of mice that survived/total</th><th colspan="5" rowspan="1" align="center" valign="bottom">Avg % day 0 body wt ± SD on indicated day p.i. (no. of mice remaining on that day)
<hr></hr></th></tr><tr><th colspan="1" rowspan="1" align="center" valign="bottom">4</th><th colspan="1" rowspan="1" align="center" valign="bottom">6</th><th colspan="1" rowspan="1" align="center" valign="bottom">8</th><th colspan="1" rowspan="1" align="center" valign="bottom">10</th><th colspan="1" rowspan="1" align="center" valign="bottom">12</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1/9</td><td colspan="1" rowspan="1" align="char" char="." valign="top">86.8 ± 4.0 (9)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">76.0 ± 3.4 (6)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">68.9 ± 3.7 (3)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">69.1 ± 8.5 (2)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">71.1 ± 12.7 (2)<xref ref-type="table-fn" rid="t1fn1"><italic>a</italic></xref></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">20</td><td colspan="1" rowspan="1" align="char" char="." valign="top">3/10</td><td colspan="1" rowspan="1" align="char" char="." valign="top">87.9 ± 6.3 (10)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">77.5 ± 6.0 (8)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">75.1 ± 3.6 (5)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">75.2 ± 7.7 (4)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">79.0 ± 13.1 (4)<xref ref-type="table-fn" rid="t1fn2"><italic>b</italic></xref></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">40</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4/9</td><td colspan="1" rowspan="1" align="char" char="." valign="top">87.0 ± 5.3 (9)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">75.6 ± 5.3 (9)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">72.2 ± 12.8 (6)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">73.4 ± 16.2 (5)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">77.1 ± 17.2 (4)</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">60</td><td colspan="1" rowspan="1" align="char" char="." valign="top">5/10</td><td colspan="1" rowspan="1" align="char" char="." valign="top">86.5 ± 4.6 (10)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">77.1 ± 4.5 (9)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">73.2 ± 9.3 (7)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">78.0 ± 11.9 (5)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">81.8 ± 14.4 (5)</td></tr></tbody></table><table-wrap-foot><fn id="t1fn1"><label>a</label><p>After day 12 there was one more death, on day 17.</p></fn><fn id="t1fn2"><label>b</label><p>After day 12 there was one more death, on day 14.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t2"><label>TABLE 2.</label><caption><p>Weight loss in mice infected with influenza virus (A/Japan/305/57) given 60 mg/kg gemfibrozil once daily from days 4 to 10 after virus exposure</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="2" align="center" valign="middle">Gemfibrozil dose (mg/kg/day)</th><th colspan="1" rowspan="2" align="center" valign="middle">No. of mice that survived/total</th><th colspan="1" rowspan="2" align="center" valign="middle">Median survival time (days)</th><th colspan="1" rowspan="2" align="center" valign="middle">95% confidence interval (days)</th><th colspan="4" rowspan="1" align="center" valign="bottom">Avg % day 0 body wt ± SD on indicated day p.i. (no. of mice remaining on that day)
<hr></hr></th></tr><tr><th colspan="1" rowspan="1" align="center" valign="bottom">6</th><th colspan="1" rowspan="1" align="center" valign="bottom">8</th><th colspan="1" rowspan="1" align="center" valign="bottom">10</th><th colspan="1" rowspan="1" align="center" valign="bottom">12</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">0</td><td colspan="1" rowspan="1" align="center" valign="top">13/50</td><td colspan="1" rowspan="1" align="center" valign="top">8</td><td colspan="1" rowspan="1" align="center" valign="top">7-10</td><td colspan="1" rowspan="1" align="char" char="." valign="top">76.1 ± 4.2 (47)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">70.3 ± 3.8 (29)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">68.3 ± 8.7 (19)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">70.8 ± 13.0 (16)<xref ref-type="table-fn" rid="t2fn2"><italic>b</italic></xref></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">60</td><td colspan="1" rowspan="1" align="center" valign="top">24/46</td><td colspan="1" rowspan="1" align="center" valign="top">NA<xref ref-type="table-fn" rid="t2fn1"><italic>a</italic></xref></td><td colspan="1" rowspan="1" align="center" valign="top">10+</td><td colspan="1" rowspan="1" align="char" char="." valign="top">76.7 ± 5.2 (45)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">71.1 ± 7.1 (36)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">71.7 ± 11.1 (30)</td><td colspan="1" rowspan="1" align="char" char="." valign="top">77.0 ± 13.4 (25)<xref ref-type="table-fn" rid="t2fn3"><italic>c</italic></xref></td></tr></tbody></table><table-wrap-foot><fn id="t2fn1"><label>a</label><p>NA, median survival time cannot be reported, as more than half the mice survived the experiment.</p></fn><fn id="t2fn2"><label>b</label><p>After day 12 there were three more deaths, two on day 13 and one on day 17.</p></fn><fn id="t2fn3"><label>c</label><p>After day 12 there was one more death, on day 13.</p></fn></table-wrap-foot></table-wrap></floats-wrap></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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