Type 4 phosphodiesterase inhibitors attenuate respiratory syncytial virus-induced airway hyper-responsiveness and lung eosinophilia.
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.
Ikemura
T
T
Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Schwarze
J
J
Makela
M
M
Kanehiro
A
A
Joetham
A
A
Ohmori
K
K
Gelfand
E W
EW
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D001992:Bronchoalveolar Lavage Fluid; D016084:Bronchoconstriction / Q000187:drug effects; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D016210:Methacholine Chloride; D051379:Mice; D008807:Mice, Inbred BALB C; D020105:Milrinone / Q000494:pharmacology; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011657:Pulmonary Eosinophilia / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D018113:Respiratory Syncytial Virus, Human; D020889:Rolipram / Q000494:pharmacology
D016207:Cytokines; D010726:Phosphodiesterase Inhibitors; D016210:Methacholine Chloride; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020105:Milrinone; D020889:Rolipram