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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

Identifieur interne : 000321 ( PascalFrancis/Corpus ); précédent : 000320; suivant : 000322

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 ; Konstantin P. Alekseev ; XINSHENG ZHANG ; Doo-Sung Cheon ; Anastasia N. Vlasova ; Linda J. Saif

Source :

RBID : Pascal:08-0025605

Descripteurs français

English descriptors

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.

Notice en format standard (ISO 2709)

Pour connaître la documentation sur le format Inist Standard.

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A08 01  1  ENG  @1 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
A11 01  1    @1 JUNG (Kwonil)
A11 02  1    @1 ALEKSEEV (Konstantin P.)
A11 03  1    @1 XINSHENG ZHANG
A11 04  1    @1 CHEON (Doo-Sung)
A11 05  1    @1 VLASOVA (Anastasia N.)
A11 06  1    @1 SAIF (Linda J.)
A14 01      @1 Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University @2 Wooster, Ohio 44691 @3 USA @Z 1 aut. @Z 2 aut. @Z 3 aut. @Z 4 aut. @Z 5 aut. @Z 6 aut.
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C01 01    ENG  @0 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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Format Inist (serveur)

NO : PASCAL 08-0025605 INIST
ET : 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
AU : JUNG (Kwonil); ALEKSEEV (Konstantin P.); XINSHENG ZHANG; CHEON (Doo-Sung); VLASOVA (Anastasia N.); SAIF (Linda J.)
AF : Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University/Wooster, Ohio 44691/Etats-Unis (1 aut., 2 aut., 3 aut., 4 aut., 5 aut., 6 aut.)
DT : Publication en série; Niveau analytique
SO : Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2007; Vol. 81; No. 24; Pp. 13681-13693; Bibl. 61 ref.
LA : Anglais
EA : 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.
CC : 002A05C10; 002A05C04
FD : Porcin; Porc; Coronavirus; Pathogénie; Animal; Immunodépresseur; Dexaméthasone; Corticostéroïde; Traitement; Aigu; Virologie; Antiinflammatoire
FG : Artiodactyla; Ungulata; Mammalia; Vertebrata; Coronaviridae; Nidovirales; Virus; Vétérinaire
ED : Swine; Pig; Coronavirus; Pathogenesis; Animal; Immunosuppressive agent; Dexamethasone; Corticosteroid; Treatment; Acute; Virology; Antiinflammatory agent
EG : Artiodactyla; Ungulata; Mammalia; Vertebrata; Coronaviridae; Nidovirales; Virus; Veterinary
SD : Porcino; Cerdo; Coronavirus; Patogenia; Animal; Inmunodepresor; Dexametasona; Corticoesteroide; Tratamiento; Agudo; Virología; Antiinflamatorio
LO : INIST-13592.354000173842080390
ID : 08-0025605

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Pascal:08-0025605

Le document en format XML

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<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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<s0>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.</s0>
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<s0>Virus</s0>
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<s0>Virus</s0>
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<NO>PASCAL 08-0025605 INIST</NO>
<ET>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</ET>
<AU>JUNG (Kwonil); ALEKSEEV (Konstantin P.); XINSHENG ZHANG; CHEON (Doo-Sung); VLASOVA (Anastasia N.); SAIF (Linda J.)</AU>
<AF>Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University/Wooster, Ohio 44691/Etats-Unis (1 aut., 2 aut., 3 aut., 4 aut., 5 aut., 6 aut.)</AF>
<DT>Publication en série; Niveau analytique</DT>
<SO>Journal of virology; ISSN 0022-538X; Etats-Unis; Da. 2007; Vol. 81; No. 24; Pp. 13681-13693; Bibl. 61 ref.</SO>
<LA>Anglais</LA>
<EA>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.</EA>
<CC>002A05C10; 002A05C04</CC>
<FD>Porcin; Porc; Coronavirus; Pathogénie; Animal; Immunodépresseur; Dexaméthasone; Corticostéroïde; Traitement; Aigu; Virologie; Antiinflammatoire</FD>
<FG>Artiodactyla; Ungulata; Mammalia; Vertebrata; Coronaviridae; Nidovirales; Virus; Vétérinaire</FG>
<ED>Swine; Pig; Coronavirus; Pathogenesis; Animal; Immunosuppressive agent; Dexamethasone; Corticosteroid; Treatment; Acute; Virology; Antiinflammatory agent</ED>
<EG>Artiodactyla; Ungulata; Mammalia; Vertebrata; Coronaviridae; Nidovirales; Virus; Veterinary</EG>
<SD>Porcino; Cerdo; Coronavirus; Patogenia; Animal; Inmunodepresor; Dexametasona; Corticoesteroide; Tratamiento; Agudo; Virología; Antiinflamatorio</SD>
<LO>INIST-13592.354000173842080390</LO>
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