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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Type 4 Phosphodiesterase Inhibitors Attenuate Respiratory Syncytial Virus-Induced Airway Hyper-Responsiveness and Lung Eosinophilia

Toshihide Ikemura, Jurgen Schwarze, Mika Makela, Arihiko Kanehiro, Anthony Joetham, Kenji Ohmori and Erwin W. Gelfand
Journal of Pharmacology and Experimental Therapeutics August 2000, 294 (2) 701-706;
Toshihide Ikemura
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Jurgen Schwarze
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Mika Makela
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Arihiko Kanehiro
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Anthony Joetham
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Kenji Ohmori
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Erwin W. Gelfand
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Abstract

Viral respiratory infections are considered one of the triggers of exacerbations of asthma. In a model of virus-induced airway hyper-responsiveness (AHR), mice infected with human respiratory syncytial virus (RSV) were shown to develop AHR accompanied by lung eosinophilia. Inhibitors of cyclic nucleotide phosphodiesterase (PDE) have been shown to affect airway responsiveness and pulmonary allergic inflammation. In this study, we assessed the effects of type 4 PDE (PDE4) inhibitors on AHR following RSV infection and compared them with a PDE3 inhibitor. In mice infected by intranasal inoculation of RSV, treatment with the PDE4 inhibitor rolipram or Ro-20-1724 reduced both AHR and the eosinophil infiltration of the airways. In contrast, the PDE3 inhibitor, milrinone, did not influence airway responsiveness or eosinophilic inflammation. These results demonstrate that PDE4 inhibitors can modulate RSV-induced AHR and lung eosinophilia and indicate that they have a potential role in treating exacerbations of asthma triggered by viral infection.

Footnotes

  • Send reprint requests to: Erwin W. Gelfand, M.D., National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206. E-mail: gelfande{at}njc.org

  • ↵1 This work was supported in part by National Institutes of Health Grants HL-61005 and HL-36577 (to E.W.G.).

  • Abbreviations:
    RSV
    respiratory syncytial virus
    AHR
    airway hyper-responsiveness
    BALF
    bronchoalveolar lavage fluid
    MCh
    methacholine
    PDE
    phosphodiesterase
    PFU
    plaque-forming units
    IFN-γ
    interferon-γ
    IL-5
    interleukin-5
    Penh
    enhanced pause
    • Received January 13, 2000.
    • Accepted April 10, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 294 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 294, Issue 2
1 Aug 2000
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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Type 4 Phosphodiesterase Inhibitors Attenuate Respiratory Syncytial Virus-Induced Airway Hyper-Responsiveness and Lung Eosinophilia

Toshihide Ikemura, Jurgen Schwarze, Mika Makela, Arihiko Kanehiro, Anthony Joetham, Kenji Ohmori and Erwin W. Gelfand
Journal of Pharmacology and Experimental Therapeutics August 1, 2000, 294 (2) 701-706;

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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Type 4 Phosphodiesterase Inhibitors Attenuate Respiratory Syncytial Virus-Induced Airway Hyper-Responsiveness and Lung Eosinophilia

Toshihide Ikemura, Jurgen Schwarze, Mika Makela, Arihiko Kanehiro, Anthony Joetham, Kenji Ohmori and Erwin W. Gelfand
Journal of Pharmacology and Experimental Therapeutics August 1, 2000, 294 (2) 701-706;
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