SrasV1, Main, Merge, bibRecord, 003926

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 : 003926 ( Main/Merge ); précédent : 003925; suivant : 003927

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▿

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.

RBID : PMC:2168842

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.
- Animaux, Coronavirus respiratoire porcin, Humains, Immunosuppression thérapeutique, Modèles animaux de maladie humaine, Résultat thérapeutique, Suidae.

English descriptors

KwdEn :
- Adrenal Cortex Hormones (administration & dosage), Adrenal Cortex Hormones (therapeutic use), Animals, Coronavirus Infections (drug therapy), Coronavirus Infections (pathology), Coronavirus Infections (physiopathology), Coronavirus Infections (virology), Dexamethasone (administration & dosage), Dexamethasone (therapeutic use), Disease Models, Animal, Humans, Immunosuppression, Lung (immunology), Lung (pathology), Lung (virology), 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 Outcome.
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 × 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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2168842

DOI: 10.1128/JVI.01702-07
PubMed: 17942563
PubMed Central: 2168842

Links to Exploration step

PMC:2168842

Le document en format XML

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<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>
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<term>Maladies des porcs (physiopathologie)</term>
<term>Maladies des porcs (traitement médicamenteux)</term>
<term>Maladies des porcs (virologie)</term>
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<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Adrenal Cortex Hormones</term>
<term>Dexamethasone</term>
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</keywords>
<keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Coronavirus respiratoire porcin</term>
</keywords>
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<term>Severe Acute Respiratory Syndrome</term>
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<term>Syndrome respiratoire aigu sévère</term>
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<term>Immunosuppression thérapeutique</term>
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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>
</TEI>
</record>

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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▿

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▿

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