Cytokine Responses in Porcine Respiratory Coronavirus-Infected Pigs Treated with Corticosteroids as a Model for Severe Acute Respiratory Syndrome▿
Identifieur interne : 000E33 ( Pmc/Checkpoint ); précédent : 000E32; suivant : 000E34Cytokine Responses in Porcine Respiratory Coronavirus-Infected Pigs Treated with Corticosteroids as a Model for Severe Acute Respiratory Syndrome▿
Auteurs : Xinsheng Zhang [États-Unis] ; Konstantin Alekseev [États-Unis] ; Kwonil Jung [États-Unis] ; Anastasia Vlasova [États-Unis] ; Nagesh Hadya [États-Unis] ; Linda J. Saif [États-Unis]Source :
- Journal of Virology [ 0022-538X ] ; 2008.
Abstract
The effectiveness and potential immunosuppressive effects of anti-inflammatory glucocorticoids in the lungs of severe acute respiratory syndrome (SARS) patients are undefined. We treated porcine respiratory coronavirus (PRCV)-infected conventional pigs with the corticosteroid dexamethasone (DEX) as a model for SARS. Innate and Th1 cytokines in bronchoalveolar lavage (BAL) and serum were elevated in PRCV-infected pigs compared to controls, but were decreased after DEX treatment in the PRCV-infected, DEX-treated (PRCV/DEX) pigs. Although decreased in BAL, Th2 cytokine levels were higher in serum after DEX treatment. Levels of the proinflammatory cytokine interleukin-6 in BAL and serum were decreased in PRCV/DEX pigs early but increased later compared to those in phosphate-buffered saline-treated, PRCV-infected pigs, corresponding to a similar trend for lung lesions. PRCV infection increased T-cell frequencies in BAL, but DEX treatment of PRCV-infected pigs reduced frequencies of T cells; interestingly B and SWC3a+ (monocytes/macrophages/granulocytes) cell frequencies were increased. DEX reduced numbers of PRCV-stimulated Th1 gamma interferon-secreting cells in spleen, tracheobroncheolar lymph nodes, and blood. Our findings suggest that future glucocorticoid treatment of SARS patients should be reconsidered in the context of potential local immunosuppression of immune responses in lung and systemic Th1 cytokine-biased suppression.
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DOI: 10.1128/JVI.02190-07
PubMed: 18287230
PubMed Central: 2293053
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xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster</wicri:cityArea></affiliation></author><author><name sortKey="Alekseev, Konstantin" sort="Alekseev, Konstantin" uniqKey="Alekseev K" first="Konstantin" last="Alekseev">Konstantin Alekseev</name><affiliation wicri:level="2"><nlm:aff id="aff0">Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio 44691</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster</wicri:cityArea></affiliation></author><author><name sortKey="Jung, Kwonil" sort="Jung, Kwonil" uniqKey="Jung K" first="Kwonil" last="Jung">Kwonil Jung</name><affiliation wicri:level="2"><nlm:aff id="aff0">Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio 44691</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster</wicri:cityArea></affiliation></author><author><name sortKey="Vlasova, Anastasia" sort="Vlasova, Anastasia" uniqKey="Vlasova A" first="Anastasia" last="Vlasova">Anastasia Vlasova</name><affiliation wicri:level="2"><nlm:aff id="aff0">Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio 44691</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster</wicri:cityArea></affiliation></author><author><name sortKey="Hadya, Nagesh" sort="Hadya, Nagesh" uniqKey="Hadya N" first="Nagesh" last="Hadya">Nagesh Hadya</name><affiliation wicri:level="2"><nlm:aff id="aff0">Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio 44691</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster</wicri:cityArea></affiliation></author><author><name sortKey="Saif, Linda J" sort="Saif, Linda J" uniqKey="Saif L" first="Linda J." last="Saif">Linda J. Saif</name><affiliation wicri:level="2"><nlm:aff id="aff0">Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio 44691</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster</wicri:cityArea></affiliation></author></analytic><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The effectiveness and potential immunosuppressive effects of anti-inflammatory glucocorticoids in the lungs of severe acute respiratory syndrome (SARS) patients are undefined. We treated porcine respiratory coronavirus (PRCV)-infected conventional pigs with the corticosteroid dexamethasone (DEX) as a model for SARS. Innate and Th1 cytokines in bronchoalveolar lavage (BAL) and serum were elevated in PRCV-infected pigs compared to controls, but were decreased after DEX treatment in the PRCV-infected, DEX-treated (PRCV/DEX) pigs. Although decreased in BAL, Th2 cytokine levels were higher in serum after DEX treatment. Levels of the proinflammatory cytokine interleukin-6 in BAL and serum were decreased in PRCV/DEX pigs early but increased later compared to those in phosphate-buffered saline-treated, PRCV-infected pigs, corresponding to a similar trend for lung lesions. PRCV infection increased T-cell frequencies in BAL, but DEX treatment of PRCV-infected pigs reduced frequencies of T cells; interestingly B and SWC3a<sup>+</sup> (monocytes/macrophages/granulocytes) cell frequencies were increased. DEX reduced numbers of PRCV-stimulated Th1 gamma interferon-secreting cells in spleen, tracheobroncheolar lymph nodes, and blood. Our findings suggest that future glucocorticoid treatment of SARS patients should be reconsidered in the context of potential local immunosuppression of immune responses in lung and systemic Th1 cytokine-biased suppression.</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">J Virol</journal-id><journal-id journal-id-type="publisher-id">jvi</journal-id><journal-title>Journal of Virology</journal-title><issn pub-type="ppub">0022-538X</issn><issn pub-type="epub">1098-5514</issn><publisher><publisher-name>American Society for Microbiology (ASM)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">18287230</article-id><article-id pub-id-type="pmc">2293053</article-id><article-id pub-id-type="publisher-id">2190-07</article-id><article-id pub-id-type="doi">10.1128/JVI.02190-07</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pathogenesis and Immunity</subject></subj-group></article-categories><title-group><article-title>Cytokine Responses in Porcine Respiratory Coronavirus-Infected Pigs Treated with Corticosteroids as a Model for Severe Acute Respiratory Syndrome<xref ref-type="fn" rid="fn1">▿</xref> </article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Xinsheng</given-names></name><xref ref-type="aff" rid="aff0"></xref></contrib><contrib contrib-type="author"><name><surname>Alekseev</surname><given-names>Konstantin</given-names></name><xref ref-type="aff" rid="aff0"></xref></contrib><contrib contrib-type="author"><name><surname>Jung</surname><given-names>Kwonil</given-names></name><xref ref-type="aff" rid="aff0"></xref></contrib><contrib contrib-type="author"><name><surname>Vlasova</surname><given-names>Anastasia</given-names></name><xref ref-type="aff" rid="aff0"></xref></contrib><contrib contrib-type="author"><name><surname>Hadya</surname><given-names>Nagesh</given-names></name><xref ref-type="aff" rid="aff0"></xref></contrib><contrib contrib-type="author"><name><surname>Saif</surname><given-names>Linda J.</given-names></name><xref ref-type="aff" rid="aff0"></xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="aff0">Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio 44691</aff><author-notes><fn id="cor1"><label>*</label><p>Corresponding author. Mailing address: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Ave., Wooster, OH 44691. Phone: (330) 263-3744. Fax: (330) 263-3677. E-mail: <email>saif.2@osu.edu</email></p></fn></author-notes><pub-date pub-type="ppub"><month>5</month><year>2008</year></pub-date><pub-date pub-type="epub"><day>20</day><month>2</month><year>2008</year></pub-date><volume>82</volume><issue>9</issue><fpage>4420</fpage><lpage>4428</lpage><history><date date-type="received"><day>5</day><month>10</month><year>2007</year></date><date date-type="accepted"><day>13</day><month>2</month><year>2008</year></date></history><permissions><copyright-statement>Copyright © 2008, American Society for Microbiology</copyright-statement></permissions><self-uri xlink:title="pdf" xlink:href="zjv00908004420.pdf"></self-uri><abstract><p>The effectiveness and potential immunosuppressive effects of anti-inflammatory glucocorticoids in the lungs of severe acute respiratory syndrome (SARS) patients are undefined. We treated porcine respiratory coronavirus (PRCV)-infected conventional pigs with the corticosteroid dexamethasone (DEX) as a model for SARS. Innate and Th1 cytokines in bronchoalveolar lavage (BAL) and serum were elevated in PRCV-infected pigs compared to controls, but were decreased after DEX treatment in the PRCV-infected, DEX-treated (PRCV/DEX) pigs. Although decreased in BAL, Th2 cytokine levels were higher in serum after DEX treatment. Levels of the proinflammatory cytokine interleukin-6 in BAL and serum were decreased in PRCV/DEX pigs early but increased later compared to those in phosphate-buffered saline-treated, PRCV-infected pigs, corresponding to a similar trend for lung lesions. PRCV infection increased T-cell frequencies in BAL, but DEX treatment of PRCV-infected pigs reduced frequencies of T cells; interestingly B and SWC3a<sup>+</sup> (monocytes/macrophages/granulocytes) cell frequencies were increased. DEX reduced numbers of PRCV-stimulated Th1 gamma interferon-secreting cells in spleen, tracheobroncheolar lymph nodes, and blood. Our findings suggest that future glucocorticoid treatment of SARS patients should be reconsidered in the context of potential local immunosuppression of immune responses in lung and systemic Th1 cytokine-biased suppression.</p></abstract></article-meta></front><floats-wrap><fig position="float" id="f1"><label>FIG. 1.</label><caption><p>Mean gross lung lesion scores of PRCV/PBS and PRCV/DEX groups. Black bars, PRCV/PBS; white bars, PRCV/DEX. Asterisks represent significant differences by Kruskal-Wallis test. Pig numbers are as follows for each of the PRCV/PBS and PRCV/DEX groups: <italic>n</italic> = 8 on PID 2, 4, 8, and 10 and <italic>n</italic> = 9 on PID 21.</p></caption><graphic xlink:href="zjv0090805250001"></graphic></fig><fig position="float" id="f2"><label>FIG. 2.</label><caption><p>Cytokine levels in the BAL of euthanized pigs. Cytokine concentrations in pg/ml are expressed as means ± standard errors. Symbols: ⧫, PRCV/PBS; ▪, PRCV/DEX; ▴, Mock/PBS; •, Mock/DEX. Pig numbers are as follows for the PRCV/PBS, PRCV/DEX, Mock/PBS, and Mock/DEX groups, respectively: <italic>n</italic> = 8, 8, 4, and 5 on PID 2; <italic>n</italic> = 8, 8, 5, and 5 on PID 4; <italic>n</italic> = 8, 8, 5, and 5 on PID 8; <italic>n</italic> = 8, 8, 4, and 4 on PID 10; and <italic>n</italic> = 9, 9, 5, and 6 on PID 21. * and # denote statistically significant difference (<italic>P</italic> < 0.05) when comparing the PRCV/PBS versus PRCV/DEX groups and PRCV-infected versus uninfected control groups, respectively, by nonparametric Kruskal-Wallis test.</p></caption><graphic xlink:href="zjv0090805250002"></graphic></fig><fig position="float" id="f3"><label>FIG. 3.</label><caption><p>Cytokine levels in the serum of euthanized pigs. Cytokine concentrations in pg/ml are expressed as means ± standard error. Symbols: ⧫, PRCV/PBS; ▪, PRCV/DEX; ▴, Mock/PBS; •, Mock/DEX. Pig numbers are as follows for the PRCV/PBS, PRCV/DEX, Mock/PBS, and Mock/DEX groups, respectively: <italic>n</italic> = 8, 8, 4, and 5 on PID 2; <italic>n</italic> = 8, 8, 5, and 5 on PID 4; <italic>n</italic> = 8, 8, 5, and 5 on PID 8; <italic>n</italic> = 8, 8, 4, and 4 on PID 10; and <italic>n</italic> = 9, 9, 5, and 6 on PID 21. * denotes statistically significant difference (<italic>P</italic> < 0.05) between the PRCV/PBS and PRCV/DEX groups by nonparametric Kruskal-Wallis test.</p></caption><graphic xlink:href="zjv0090805250003"></graphic></fig><fig position="float" id="f4"><label>FIG. 4.</label><caption><p>IFN-γ CSC in spleen, TBLN, and blood of euthanized pigs. Symbols: ⧫, PRCV/PBS; ▪, PRCV/DEX; ▴ (triangles), Mock/PBS; •, Mock/DEX. Pig numbers are as follows for the PRCV/PBS, PRCV/DEX, Mock/PBS, and Mock/DEX groups, respectively: <italic>n</italic> = 8, 8, 4, and 5 on PID 2; <italic>n</italic> = 8, 8, 5, and 5 on PID 4; <italic>n</italic> = 8, 8, 5, and 5 on PID 8; <italic>n</italic> = 8, 8, 4, and 4 on PID 10; and <italic>n</italic> = 9, 9, 5, and 6 on PID 21. * denotes statistically significant difference (<italic>P</italic> < 0.05) between the PRCV/PBS and PRCV/DEX groups by nonparametric Kruskal-Wallis test.</p></caption><graphic xlink:href="zjv0090805250004"></graphic></fig><fig position="float" id="f5"><label>FIG. 5.</label><caption><p>Frequencies of CD3<sup>+</sup>, CD4<sup>+</sup>, CD8<sup>+</sup>, and CD21<sup>+</sup> lymphocytes and SWC3a<sup>+</sup> cells in total BAL cells of euthanized pigs. Bars: black, PRCV/PBS; white, PRCV/DEX; dashed, Mock/PBS; dotted, Mock/DEX. Pig numbers are as follows for the PRCV/PBS, PRCV/DEX, Mock/PBS, and Mock/DEX groups, respectively: <italic>n</italic> = 8, 8, 4, and 5 on PID 2; <italic>n</italic> = 8, 8, 5, and 5 on PID 4; <italic>n</italic> = 8, 8, 5, and 5 on PID 8; <italic>n</italic> = 8, 8, 4, and 4 on PID 10; and <italic>n</italic> = 9, 9, 5, and 6 on PID 21. * and # denote statistically significant difference (<italic>P</italic> < 0.05) when comparing the PRCV/PBS versus PRCV/DEX groups and Mock/PBS versus Mock/DEX groups, respectively, by nonparametric Kruskal-Wallis test.</p></caption><graphic xlink:href="zjv0090805250005"></graphic></fig></floats-wrap></pmc><affiliations><list><country><li>États-Unis</li></country><region><li>Ohio</li></region></list><tree><country name="États-Unis"><region name="Ohio"><name sortKey="Zhang, Xinsheng" sort="Zhang, Xinsheng" uniqKey="Zhang X" first="Xinsheng" last="Zhang">Xinsheng Zhang</name></region><name sortKey="Alekseev, Konstantin" sort="Alekseev, Konstantin" uniqKey="Alekseev K" first="Konstantin" last="Alekseev">Konstantin Alekseev</name><name sortKey="Hadya, Nagesh" sort="Hadya, Nagesh" uniqKey="Hadya N" first="Nagesh" last="Hadya">Nagesh Hadya</name><name sortKey="Jung, Kwonil" sort="Jung, Kwonil" uniqKey="Jung K" first="Kwonil" last="Jung">Kwonil Jung</name><name sortKey="Saif, Linda J" sort="Saif, Linda J" uniqKey="Saif L" first="Linda J." last="Saif">Linda J. Saif</name><name sortKey="Vlasova, Anastasia" sort="Vlasova, Anastasia" uniqKey="Vlasova A" first="Anastasia" last="Vlasova">Anastasia Vlasova</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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