Altered Pathogenesis of Porcine Respiratory Coronavirus in Pigs due to Immunosuppressive Effects of Dexamethasone : Implications for Corticosteroid Use in Treatment of Severe Acute Respiratory Syndrome Coronavirus
Identifieur interne : 003B90 ( Main/Curation ); précédent : 003B89; suivant : 003B91Altered Pathogenesis of Porcine Respiratory Coronavirus in Pigs due to Immunosuppressive Effects of Dexamethasone : Implications for Corticosteroid Use in Treatment of Severe Acute Respiratory Syndrome Coronavirus
Auteurs : Kwonil Jung [États-Unis] ; Konstantin P. Alekseev [États-Unis] ; XINSHENG ZHANG [États-Unis] ; Doo-Sung Cheon [États-Unis] ; Anastasia N. Vlasova [États-Unis] ; Linda J. Saif [États-Unis]Source :
- Journal of virology [ 0022-538X ] ; 2007.
Descripteurs français
- KwdFr :
- Animaux, Coronavirus respiratoire porcin (), Coronavirus respiratoire porcin (génétique), Coronavirus respiratoire porcin (isolement et purification), Coronavirus respiratoire porcin (pathogénicité), Dexaméthasone (administration et posologie), Dexaméthasone (usage thérapeutique), Hormones corticosurrénaliennes (administration et posologie), Hormones corticosurrénaliennes (usage thérapeutique), Humains, Immunosuppression thérapeutique, Infections à coronavirus (anatomopathologie), Infections à coronavirus (physiopathologie), Infections à coronavirus (traitement médicamenteux), Infections à coronavirus (virologie), Maladies des porcs (anatomopathologie), Maladies des porcs (physiopathologie), Maladies des porcs (traitement médicamenteux), Maladies des porcs (virologie), Modèles animaux de maladie humaine, Poumon (anatomopathologie), Poumon (immunologie), Poumon (virologie), Résultat thérapeutique, Suidae, Syndrome respiratoire aigu sévère (anatomopathologie), Syndrome respiratoire aigu sévère (physiopathologie), Syndrome respiratoire aigu sévère (traitement médicamenteux), Syndrome respiratoire aigu sévère (virologie).
- MESH :
- administration et posologie : Dexaméthasone, Hormones corticosurrénaliennes.
- anatomopathologie : Infections à coronavirus, Maladies des porcs, Poumon, Syndrome respiratoire aigu sévère.
- génétique : Coronavirus respiratoire porcin.
- immunologie : Poumon.
- isolement et purification : Coronavirus respiratoire porcin.
- pathogénicité : Coronavirus respiratoire porcin.
- physiopathologie : Infections à coronavirus, Maladies des porcs, Syndrome respiratoire aigu sévère.
- traitement médicamenteux : Infections à coronavirus, Maladies des porcs, Syndrome respiratoire aigu sévère.
- usage thérapeutique : Dexaméthasone, Hormones corticosurrénaliennes.
- virologie : Infections à coronavirus, Maladies des porcs, Poumon, Syndrome respiratoire aigu sévère.
- Pascal (Inist)
- Wicri :
- topic : Porcin.
English descriptors
- KwdEn :
- Acute, Adrenal Cortex Hormones (administration & dosage), Adrenal Cortex Hormones (therapeutic use), Animal, Animals, Antiinflammatory agent, Coronavirus, Coronavirus Infections (drug therapy), Coronavirus Infections (pathology), Coronavirus Infections (physiopathology), Coronavirus Infections (virology), Corticosteroid, Dexamethasone, Dexamethasone (administration & dosage), Dexamethasone (therapeutic use), Disease Models, Animal, Humans, Immunosuppression, Immunosuppressive agent, Lung (immunology), Lung (pathology), Lung (virology), Pathogenesis, Pig, Porcine Respiratory Coronavirus (drug effects), Porcine Respiratory Coronavirus (genetics), Porcine Respiratory Coronavirus (isolation & purification), Porcine Respiratory Coronavirus (pathogenicity), Severe Acute Respiratory Syndrome (drug therapy), Severe Acute Respiratory Syndrome (pathology), Severe Acute Respiratory Syndrome (physiopathology), Severe Acute Respiratory Syndrome (virology), Swine, Swine Diseases (drug therapy), Swine Diseases (pathology), Swine Diseases (physiopathology), Swine Diseases (virology), Treatment, Treatment Outcome, Virology.
- MESH :
- chemical , administration & dosage : Adrenal Cortex Hormones, Dexamethasone.
- chemical , therapeutic use : Adrenal Cortex Hormones, Dexamethasone.
- drug effects : Porcine Respiratory Coronavirus.
- drug therapy : Coronavirus Infections, Severe Acute Respiratory Syndrome, Swine Diseases.
- genetics : Porcine Respiratory Coronavirus.
- immunology : Lung.
- isolation & purification : Porcine Respiratory Coronavirus.
- pathogenicity : Porcine Respiratory Coronavirus.
- pathology : Coronavirus Infections, Lung, Severe Acute Respiratory Syndrome, Swine Diseases.
- physiopathology : Coronavirus Infections, Severe Acute Respiratory Syndrome, Swine Diseases.
- virology : Coronavirus Infections, Lung, Severe Acute Respiratory Syndrome, Swine Diseases.
- Animals, Disease Models, Animal, Humans, Immunosuppression, Swine, Treatment Outcome.
Abstract
The pathogenesis and optimal treatments for severe acute respiratory syndrome (SARS) are unclear, although corticosteroids were used to reduce lung and systemic inflammation. Because the pulmonary pathology of porcine respiratory coronavirus (PRCV) in pigs resembles SARS, we used PRCV as a model to clarify the effects of the corticosteroid dexamethasone (DEX) on coronavirus (CoV)-induced pneumonia. Conventional weaned pigs (n = 130) in one of four groups (PRCV/phosphate-buffered saline [PBS] [n = 41], PRCV/DEX [n = 41], mock/PBS [n = 23], and mock/DEX [n = 25]) were inoculated intranasally and intratracheally with the ISU-1 strain of PRCV (1 x 107 PFU) or cell culture medium. DEX was administered (once daily, 2 mg/kg of body weight/day, intramuscularly) from postinoculation day (PID) 1 to 6. In PRCV/DEX pigs, significantly milder pneumonia, fewer PRCV-positive cells, and lower viral RNA titers were present in lungs early at PID 2; however, at PID 4, 10, and 21, severe bronchointerstitial pneumonia, significantly higher numbers of PRCV-positive cells, and higher viral RNA titers were observed compared to results for PRCV/PBS pigs. Significantly lower numbers of CD2+, CD3+, CD4+, and CD8+ T cells were also observed in lungs of PRCV/DEX pigs than in those of PRCV/PBS pigs at PID 8 and 10, coincident with fewer gamma interferon (IFN-γ)-secreting cells in the tracheobronchial lymph nodes as determined by enzyme-linked immunospot assay. Our results confirm that DEX treatment alleviates PRCV pneumonia early (PID 2) in the infection but continued use through PID 6 exacerbates later stages of infection (PID 4, 10, and 21), possibly by decreasing cellular immune responses in the lungs (IFN-γ-secreting T cells), thereby creating an environment for more-extensive viral replication. These data have potential implications for corticosteroid use with SARS-CoV patients and suggest a precaution against prolonged use based on their unproven efficacy in humans, including possible detrimental secondary effects.
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<term>Adrenal Cortex Hormones (administration & dosage)</term>
<term>Adrenal Cortex Hormones (therapeutic use)</term>
<term>Animal</term>
<term>Animals</term>
<term>Antiinflammatory agent</term>
<term>Coronavirus</term>
<term>Coronavirus Infections (drug therapy)</term>
<term>Coronavirus Infections (pathology)</term>
<term>Coronavirus Infections (physiopathology)</term>
<term>Coronavirus Infections (virology)</term>
<term>Corticosteroid</term>
<term>Dexamethasone</term>
<term>Dexamethasone (administration & dosage)</term>
<term>Dexamethasone (therapeutic use)</term>
<term>Disease Models, Animal</term>
<term>Humans</term>
<term>Immunosuppression</term>
<term>Immunosuppressive agent</term>
<term>Lung (immunology)</term>
<term>Lung (pathology)</term>
<term>Lung (virology)</term>
<term>Pathogenesis</term>
<term>Pig</term>
<term>Porcine Respiratory Coronavirus (drug effects)</term>
<term>Porcine Respiratory Coronavirus (genetics)</term>
<term>Porcine Respiratory Coronavirus (isolation & purification)</term>
<term>Porcine Respiratory Coronavirus (pathogenicity)</term>
<term>Severe Acute Respiratory Syndrome (drug therapy)</term>
<term>Severe Acute Respiratory Syndrome (pathology)</term>
<term>Severe Acute Respiratory Syndrome (physiopathology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Swine</term>
<term>Swine Diseases (drug therapy)</term>
<term>Swine Diseases (pathology)</term>
<term>Swine Diseases (physiopathology)</term>
<term>Swine Diseases (virology)</term>
<term>Treatment</term>
<term>Treatment Outcome</term>
<term>Virology</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Coronavirus respiratoire porcin ()</term>
<term>Coronavirus respiratoire porcin (génétique)</term>
<term>Coronavirus respiratoire porcin (isolement et purification)</term>
<term>Coronavirus respiratoire porcin (pathogénicité)</term>
<term>Dexaméthasone (administration et posologie)</term>
<term>Dexaméthasone (usage thérapeutique)</term>
<term>Hormones corticosurrénaliennes (administration et posologie)</term>
<term>Hormones corticosurrénaliennes (usage thérapeutique)</term>
<term>Humains</term>
<term>Immunosuppression thérapeutique</term>
<term>Infections à coronavirus (anatomopathologie)</term>
<term>Infections à coronavirus (physiopathologie)</term>
<term>Infections à coronavirus (traitement médicamenteux)</term>
<term>Infections à coronavirus (virologie)</term>
<term>Maladies des porcs (anatomopathologie)</term>
<term>Maladies des porcs (physiopathologie)</term>
<term>Maladies des porcs (traitement médicamenteux)</term>
<term>Maladies des porcs (virologie)</term>
<term>Modèles animaux de maladie humaine</term>
<term>Poumon (anatomopathologie)</term>
<term>Poumon (immunologie)</term>
<term>Poumon (virologie)</term>
<term>Résultat thérapeutique</term>
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<term>Syndrome respiratoire aigu sévère (anatomopathologie)</term>
<term>Syndrome respiratoire aigu sévère (physiopathologie)</term>
<term>Syndrome respiratoire aigu sévère (traitement médicamenteux)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Adrenal Cortex Hormones</term>
<term>Dexamethasone</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Adrenal Cortex Hormones</term>
<term>Dexamethasone</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Dexaméthasone</term>
<term>Hormones corticosurrénaliennes</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Maladies des porcs</term>
<term>Poumon</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Porcine Respiratory Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term>
<term>Severe Acute Respiratory Syndrome</term>
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<front><div type="abstract" xml:lang="en">The pathogenesis and optimal treatments for severe acute respiratory syndrome (SARS) are unclear, although corticosteroids were used to reduce lung and systemic inflammation. Because the pulmonary pathology of porcine respiratory coronavirus (PRCV) in pigs resembles SARS, we used PRCV as a model to clarify the effects of the corticosteroid dexamethasone (DEX) on coronavirus (CoV)-induced pneumonia. Conventional weaned pigs (n = 130) in one of four groups (PRCV/phosphate-buffered saline [PBS] [n = 41], PRCV/DEX [n = 41], mock/PBS [n = 23], and mock/DEX [n = 25]) were inoculated intranasally and intratracheally with the ISU-1 strain of PRCV (1 x 10<sup>7</sup>
PFU) or cell culture medium. DEX was administered (once daily, 2 mg/kg of body weight/day, intramuscularly) from postinoculation day (PID) 1 to 6. In PRCV/DEX pigs, significantly milder pneumonia, fewer PRCV-positive cells, and lower viral RNA titers were present in lungs early at PID 2; however, at PID 4, 10, and 21, severe bronchointerstitial pneumonia, significantly higher numbers of PRCV-positive cells, and higher viral RNA titers were observed compared to results for PRCV/PBS pigs. Significantly lower numbers of CD2<sup>+</sup>
, CD3<sup>+</sup>
, CD4<sup>+</sup>
, and CD8<sup>+</sup>
T cells were also observed in lungs of PRCV/DEX pigs than in those of PRCV/PBS pigs at PID 8 and 10, coincident with fewer gamma interferon (IFN-γ)-secreting cells in the tracheobronchial lymph nodes as determined by enzyme-linked immunospot assay. Our results confirm that DEX treatment alleviates PRCV pneumonia early (PID 2) in the infection but continued use through PID 6 exacerbates later stages of infection (PID 4, 10, and 21), possibly by decreasing cellular immune responses in the lungs (IFN-γ-secreting T cells), thereby creating an environment for more-extensive viral replication. These data have potential implications for corticosteroid use with SARS-CoV patients and suggest a precaution against prolonged use based on their unproven efficacy in humans, including possible detrimental secondary effects.</div>
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<front><div type="abstract" xml:lang="en">The pathogenesis and optimal treatments for severe acute respiratory syndrome (SARS) are unclear, although corticosteroids were used to reduce lung and systemic inflammation. Because the pulmonary pathology of porcine respiratory coronavirus (PRCV) in pigs resembles SARS, we used PRCV as a model to clarify the effects of the corticosteroid dexamethasone (DEX) on coronavirus (CoV)-induced pneumonia. Conventional weaned pigs (n = 130) in one of four groups (PRCV/phosphate-buffered saline [PBS] [n = 41], PRCV/DEX [n = 41], mock/PBS [n = 23], and mock/DEX [n = 25]) were inoculated intranasally and intratracheally with the ISU-1 strain of PRCV (1 x 10<sup>7</sup>
PFU) or cell culture medium. DEX was administered (once daily, 2 mg/kg of body weight/day, intramuscularly) from postinoculation day (PID) 1 to 6. In PRCV/DEX pigs, significantly milder pneumonia, fewer PRCV-positive cells, and lower viral RNA titers were present in lungs early at PID 2; however, at PID 4, 10, and 21, severe bronchointerstitial pneumonia, significantly higher numbers of PRCV-positive cells, and higher viral RNA titers were observed compared to results for PRCV/PBS pigs. Significantly lower numbers of CD2<sup>+</sup>
, CD3<sup>+</sup>
, CD4<sup>+</sup>
, and CD8<sup>+</sup>
T cells were also observed in lungs of PRCV/DEX pigs than in those of PRCV/PBS pigs at PID 8 and 10, coincident with fewer gamma interferon (IFN-γ)-secreting cells in the tracheobronchial lymph nodes as determined by enzyme-linked immunospot assay. Our results confirm that DEX treatment alleviates PRCV pneumonia early (PID 2) in the infection but continued use through PID 6 exacerbates later stages of infection (PID 4, 10, and 21), possibly by decreasing cellular immune responses in the lungs (IFN-γ-secreting T cells), thereby creating an environment for more-extensive viral replication. These data have potential implications for corticosteroid use with SARS-CoV patients and suggest a precaution against prolonged use based on their unproven efficacy in humans, including possible detrimental secondary effects.</div>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Altered Pathogenesis of Porcine Respiratory Coronavirus in Pigs due to Immunosuppressive Effects of Dexamethasone: Implications for Corticosteroid Use in Treatment of Severe Acute Respiratory Syndrome Coronavirus<xref ref-type="fn" rid="fn1">▿</xref>
</title>
<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, 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, The Ohio State University, Wooster</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Alekseev, Konstantin P" sort="Alekseev, Konstantin P" uniqKey="Alekseev K" first="Konstantin P." last="Alekseev">Konstantin P. Alekseev</name>
<affiliation wicri:level="2"><nlm:aff id="aff0">Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 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, The Ohio State University, Wooster</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Zhang, Xinsheng" sort="Zhang, Xinsheng" uniqKey="Zhang X" first="Xinsheng" last="Zhang">Xinsheng Zhang</name>
<affiliation wicri:level="2"><nlm:aff id="aff0">Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 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, The Ohio State University, Wooster</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Cheon, Doo Sung" sort="Cheon, Doo Sung" uniqKey="Cheon D" first="Doo-Sung" last="Cheon">Doo-Sung Cheon</name>
<affiliation wicri:level="2"><nlm:aff id="aff0">Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 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, The Ohio State University, Wooster</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Vlasova, Anastasia N" sort="Vlasova, Anastasia N" uniqKey="Vlasova A" first="Anastasia N." last="Vlasova">Anastasia N. Vlasova</name>
<affiliation wicri:level="2"><nlm:aff id="aff0">Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 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, 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, 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, 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="2007">2007</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adrenal Cortex Hormones (administration & dosage)</term>
<term>Adrenal Cortex Hormones (therapeutic use)</term>
<term>Animals</term>
<term>Coronavirus Infections (drug therapy)</term>
<term>Coronavirus Infections (pathology)</term>
<term>Coronavirus Infections (physiopathology)</term>
<term>Coronavirus Infections (virology)</term>
<term>Dexamethasone (administration & dosage)</term>
<term>Dexamethasone (therapeutic use)</term>
<term>Disease Models, Animal</term>
<term>Humans</term>
<term>Immunosuppression</term>
<term>Lung (immunology)</term>
<term>Lung (pathology)</term>
<term>Lung (virology)</term>
<term>Porcine Respiratory Coronavirus (drug effects)</term>
<term>Porcine Respiratory Coronavirus (genetics)</term>
<term>Porcine Respiratory Coronavirus (isolation & purification)</term>
<term>Porcine Respiratory Coronavirus (pathogenicity)</term>
<term>Severe Acute Respiratory Syndrome (drug therapy)</term>
<term>Severe Acute Respiratory Syndrome (pathology)</term>
<term>Severe Acute Respiratory Syndrome (physiopathology)</term>
<term>Severe Acute Respiratory Syndrome (virology)</term>
<term>Swine</term>
<term>Swine Diseases (drug therapy)</term>
<term>Swine Diseases (pathology)</term>
<term>Swine Diseases (physiopathology)</term>
<term>Swine Diseases (virology)</term>
<term>Treatment Outcome</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Coronavirus respiratoire porcin ()</term>
<term>Coronavirus respiratoire porcin (génétique)</term>
<term>Coronavirus respiratoire porcin (isolement et purification)</term>
<term>Coronavirus respiratoire porcin (pathogénicité)</term>
<term>Dexaméthasone (administration et posologie)</term>
<term>Dexaméthasone (usage thérapeutique)</term>
<term>Hormones corticosurrénaliennes (administration et posologie)</term>
<term>Hormones corticosurrénaliennes (usage thérapeutique)</term>
<term>Humains</term>
<term>Immunosuppression thérapeutique</term>
<term>Infections à coronavirus (anatomopathologie)</term>
<term>Infections à coronavirus (physiopathologie)</term>
<term>Infections à coronavirus (traitement médicamenteux)</term>
<term>Infections à coronavirus (virologie)</term>
<term>Maladies des porcs (anatomopathologie)</term>
<term>Maladies des porcs (physiopathologie)</term>
<term>Maladies des porcs (traitement médicamenteux)</term>
<term>Maladies des porcs (virologie)</term>
<term>Modèles animaux de maladie humaine</term>
<term>Poumon (anatomopathologie)</term>
<term>Poumon (immunologie)</term>
<term>Poumon (virologie)</term>
<term>Résultat thérapeutique</term>
<term>Suidae</term>
<term>Syndrome respiratoire aigu sévère (anatomopathologie)</term>
<term>Syndrome respiratoire aigu sévère (physiopathologie)</term>
<term>Syndrome respiratoire aigu sévère (traitement médicamenteux)</term>
<term>Syndrome respiratoire aigu sévère (virologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Adrenal Cortex Hormones</term>
<term>Dexamethasone</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Adrenal Cortex Hormones</term>
<term>Dexamethasone</term>
</keywords>
<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Dexaméthasone</term>
<term>Hormones corticosurrénaliennes</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Maladies des porcs</term>
<term>Poumon</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Porcine Respiratory Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Coronavirus Infections</term>
<term>Severe Acute Respiratory Syndrome</term>
<term>Swine Diseases</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Porcine Respiratory Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Coronavirus respiratoire porcin</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Lung</term>
</keywords>
<keywords scheme="MESH" qualifier="isolation & purification" xml:lang="en"><term>Porcine Respiratory Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Coronavirus respiratoire porcin</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Porcine Respiratory Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Coronavirus respiratoire porcin</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Lung</term>
<term>Severe Acute Respiratory Syndrome</term>
<term>Swine Diseases</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Maladies des porcs</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Severe Acute Respiratory Syndrome</term>
<term>Swine Diseases</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Maladies des porcs</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Dexaméthasone</term>
<term>Hormones corticosurrénaliennes</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Maladies des porcs</term>
<term>Poumon</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Coronavirus Infections</term>
<term>Lung</term>
<term>Severe Acute Respiratory Syndrome</term>
<term>Swine Diseases</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Disease Models, Animal</term>
<term>Humans</term>
<term>Immunosuppression</term>
<term>Swine</term>
<term>Treatment Outcome</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Coronavirus respiratoire porcin</term>
<term>Humains</term>
<term>Immunosuppression thérapeutique</term>
<term>Modèles animaux de maladie humaine</term>
<term>Résultat thérapeutique</term>
<term>Suidae</term>
</keywords>
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<front><div type="abstract" xml:lang="en"><p>The pathogenesis and optimal treatments for severe acute respiratory syndrome (SARS) are unclear, although corticosteroids were used to reduce lung and systemic inflammation. Because the pulmonary pathology of porcine respiratory coronavirus (PRCV) in pigs resembles SARS, we used PRCV as a model to clarify the effects of the corticosteroid dexamethasone (DEX) on coronavirus (CoV)-induced pneumonia. Conventional weaned pigs (<italic>n</italic>
= 130) in one of four groups (PRCV/phosphate-buffered saline [PBS] [<italic>n</italic>
= 41], PRCV/DEX [<italic>n</italic>
= 41], mock/PBS [<italic>n</italic>
= 23], and mock/DEX [<italic>n</italic>
= 25]) were inoculated intranasally and intratracheally with the ISU-1 strain of PRCV (1 × 10<sup>7</sup>
PFU) or cell culture medium. DEX was administered (once daily, 2 mg/kg of body weight/day, intramuscularly) from postinoculation day (PID) 1 to 6. In PRCV/DEX pigs, significantly milder pneumonia, fewer PRCV-positive cells, and lower viral RNA titers were present in lungs early at PID 2; however, at PID 4, 10, and 21, severe bronchointerstitial pneumonia, significantly higher numbers of PRCV-positive cells, and higher viral RNA titers were observed compared to results for PRCV/PBS pigs. Significantly lower numbers of CD2<sup>+</sup>
, CD3<sup>+</sup>
, CD4<sup>+</sup>
, and CD8<sup>+</sup>
T cells were also observed in lungs of PRCV/DEX pigs than in those of PRCV/PBS pigs at PID 8 and 10, coincident with fewer gamma interferon (IFN-γ)-secreting cells in the tracheobronchial lymph nodes as determined by enzyme-linked immunospot assay. Our results confirm that DEX treatment alleviates PRCV pneumonia early (PID 2) in the infection but continued use through PID 6 exacerbates later stages of infection (PID 4, 10, and 21), possibly by decreasing cellular immune responses in the lungs (IFN-γ-secreting T cells), thereby creating an environment for more-extensive viral replication. These data have potential implications for corticosteroid use with SARS-CoV patients and suggest a precaution against prolonged use based on their unproven efficacy in humans, including possible detrimental secondary effects.</p>
</div>
</front>
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