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
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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
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↵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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