The effect of selective phosphodiesterase inhibitors in comparison with other anti-asthma drugs on allergen-induced eosinophilia in guinea-pig airways.
The effects of isoenzyme selective phosphodiesterase (PDE) inhibitors and other anti-asthma drugs on antigen-induced eosinophil recruitment and activation in guinea-pig airways was studied. Guinea-pigs were sensitized and subsequently challenged with aerosolized ovalbumin (OVA). Bronchoalveolar lavage (BAL) was performed 24 h later. A significant increase in eosinophils and eosinophil peroxidase (EPO) was detected in BAL fluid and BAL fluid supernatant respectively from OVA immunized guinea-pigs compared with sham treated animals. Guinea-pigs were treated for 7 days prior to antigen challenge with either the following drugs or the appropriate vehicle (i.p.). The selective beta 2 agonist, salbutamol (0.3 mg/kg), the PDE III inhibitor, milrinone (15 mg/kg) and the non-selective PDE inhibitor, trequinsin (1 mg/kg) had no effect on eosinophil number or EPO levels. The PDE IV inhibitor, rolipram (15 mg/kg), the mixed type III/IV PDE inhibitor, benzafentrine (15 mg/kg) and the non-selective PDE inhibitor, aminophylline (31.5 mg/kg) had no effect on eosinophil number but reduced the amount of EPO detected. The anti-inflammatory glucocorticosteroids, beclomethasone (10 mg/kg) and betamethasone (4 mg/kg) and the type IV PDE inhibitor, RP 73401 (5 mg/kg) reduced both eosinophil numbers and EPO levels. These results suggest a role for the type IV PDE isoenzyme in the control of eosinophil recruitment and possibly activation in the airways.
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Department of Pharmacology, King's College London, UK.
Marchini
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Buschi
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Moriggi
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Semeraro
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D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000485:Allergens / Q000276:immunology*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D047209:Eosinophil Peroxidase; D004802:Eosinophilia / Q000517:prevention & control*; D006168:Guinea Pigs; D008297:Male; D010544:Peroxidases / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D000485:Allergens; D018927:Anti-Asthmatic Agents; D001549:Benzamides; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; D047209:Eosinophil Peroxidase; D010544:Peroxidases; C087566:piclamilast