Vol. 294, Issue 2, 701-706, August 2000

Type 4 Phosphodiesterase Inhibitors Attenuate Respiratory Syncytial Virus-Induced Airway Hyper-Responsiveness and Lung Eosinophilia¹

Toshihide Ikemura, Jurgen Schwarze, Mika Makela, Arihiko Kanehiro, Anthony Joetham, Kenji Ohmori and Erwin W. Gelfand

Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado (T.I., J.S., M.M., A.K., A.J., E.W.G.); and Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo, Shizuoka, Japan (K.O.)

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.