Chloroquine Enhances Survival in Bacillus anthracis Intoxication
Identifieur interne : 001F28 ( Main/Exploration ); précédent : 001F27; suivant : 001F29Chloroquine Enhances Survival in Bacillus anthracis Intoxication
Auteurs : Andrew W. Artenstein [États-Unis] ; Steven M. Opal [États-Unis] ; Patricia Cristofaro [États-Unis] ; John E. Palardy [États-Unis] ; Nicolas A. Parejo [États-Unis] ; Michael D. Green [Géorgie (pays)] ; Jhung W. Jhung [États-Unis]Source :
- Journal of Infectious Diseases [ 0022-1899 ] ; 2004.
Abstract
The intentional release of anthrax in the United States in 2001 resulted in 11 cases of inhalational disease, with an attendant mortality rate of 45%. Current therapeutic options for anthrax are limited; antimicrobials target only replicating organisms, thus allowing bacterial toxins to cause unchecked, devastating physiological derangements in the host. Novel approaches that target the cytotoxic effects of anthrax exotoxins are needed. Chloroquine (CQ), a commonly used antimalarial agent, endows anthrax-intoxicated murine peritoneal macrophages with a 50% and 35% marginal survival advantage at 2 and 4 h, respectively, over that of untreated control cells. The cell rescue is dose dependent and, at lower concentrations, results in delayed cell death. We subsequently studied the effect of CQ in BALB/c mice challenged with anthrax lethal toxin. CQ-treated mice demonstrated reduced tissue injury, as assessed by histopathological examination of the spleen and by peripheral blood differential cell count ratios. CQ significantly enhanced survival and may augment current treatment and prophylaxis options for this otherwise lethal infection.
Url:
DOI: 10.1086/424853
Affiliations:
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Palardy</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Rhode Island</region></placeName><wicri:cityArea>Center for Biodefense and Emerging Pathogens, Division of Infectious Diseases, Providence</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Rhode Island</region></placeName><wicri:cityArea>Brown Medical School, Providence</wicri:cityArea></affiliation></author><author><name sortKey="Parejo, Nicolas A" sort="Parejo, Nicolas A" uniqKey="Parejo N" first="Nicolas A." last="Parejo">Nicolas A. 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Jhung</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Rhode Island</region></placeName><wicri:cityArea>Department of Anatomic Pathology, Memorial Hospital of Rhode Island, Pawtucket, Providence</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Infectious Diseases</title><title level="j" type="abbrev">J Infect Dis.</title><idno type="ISSN">0022-1899</idno><idno type="eISSN">1537-6613</idno><imprint><publisher>The University of Chicago Press</publisher><date when="2004-11-01">2004</date><biblScope unit="vol">190</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="1655">1655</biblScope><biblScope unit="page" to="1660">1660</biblScope></imprint><idno type="ISSN">0022-1899</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-1899</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">The intentional release of anthrax in the United States in 2001 resulted in 11 cases of inhalational disease, with an attendant mortality rate of 45%. Current therapeutic options for anthrax are limited; antimicrobials target only replicating organisms, thus allowing bacterial toxins to cause unchecked, devastating physiological derangements in the host. Novel approaches that target the cytotoxic effects of anthrax exotoxins are needed. Chloroquine (CQ), a commonly used antimalarial agent, endows anthrax-intoxicated murine peritoneal macrophages with a 50% and 35% marginal survival advantage at 2 and 4 h, respectively, over that of untreated control cells. The cell rescue is dose dependent and, at lower concentrations, results in delayed cell death. We subsequently studied the effect of CQ in BALB/c mice challenged with anthrax lethal toxin. CQ-treated mice demonstrated reduced tissue injury, as assessed by histopathological examination of the spleen and by peripheral blood differential cell count ratios. CQ significantly enhanced survival and may augment current treatment and prophylaxis options for this otherwise lethal infection.</div></front></TEI><affiliations><list><country><li>Géorgie (pays)</li><li>États-Unis</li></country><region><li>Rhode Island</li></region></list><tree><country name="États-Unis"><region name="Rhode Island"><name sortKey="Artenstein, Andrew W" sort="Artenstein, Andrew W" uniqKey="Artenstein A" first="Andrew W." last="Artenstein">Andrew W. Artenstein</name></region><name sortKey="Artenstein, Andrew W" sort="Artenstein, Andrew W" uniqKey="Artenstein A" first="Andrew W." last="Artenstein">Andrew W. Artenstein</name><name sortKey="Artenstein, Andrew W" sort="Artenstein, Andrew W" uniqKey="Artenstein A" first="Andrew W." last="Artenstein">Andrew W. Artenstein</name><name sortKey="Artenstein, Andrew W" sort="Artenstein, Andrew W" uniqKey="Artenstein A" first="Andrew W." last="Artenstein">Andrew W. Artenstein</name><name sortKey="Cristofaro, Patricia" sort="Cristofaro, Patricia" uniqKey="Cristofaro P" first="Patricia" last="Cristofaro">Patricia Cristofaro</name><name sortKey="Cristofaro, Patricia" sort="Cristofaro, Patricia" uniqKey="Cristofaro P" first="Patricia" last="Cristofaro">Patricia Cristofaro</name><name sortKey="Jhung, Jhung W" sort="Jhung, Jhung W" uniqKey="Jhung J" first="Jhung W." last="Jhung">Jhung W. Jhung</name><name sortKey="Opal, Steven M" sort="Opal, Steven M" uniqKey="Opal S" first="Steven M." last="Opal">Steven M. Opal</name><name sortKey="Opal, Steven M" sort="Opal, Steven M" uniqKey="Opal S" first="Steven M." last="Opal">Steven M. Opal</name><name sortKey="Palardy, John E" sort="Palardy, John E" uniqKey="Palardy J" first="John E." last="Palardy">John E. Palardy</name><name sortKey="Palardy, John E" sort="Palardy, John E" uniqKey="Palardy J" first="John E." last="Palardy">John E. Palardy</name><name sortKey="Parejo, Nicolas A" sort="Parejo, Nicolas A" uniqKey="Parejo N" first="Nicolas A." last="Parejo">Nicolas A. Parejo</name><name sortKey="Parejo, Nicolas A" sort="Parejo, Nicolas A" uniqKey="Parejo N" first="Nicolas A." last="Parejo">Nicolas A. Parejo</name></country><country name="Géorgie (pays)"><noRegion><name sortKey="Green, Michael D" sort="Green, Michael D" uniqKey="Green M" first="Michael D." last="Green">Michael D. Green</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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