The Effect of Selective Phosphodiesterase Inhibitors in Comparison with other Anti-asthma Drugs on Allergen-induced Eosinophilia in Guinea-pig Airways
✍ Scribed by K.H. Banner; F. Marchini; A. Buschi; E. Moriggi; C. Semeraro; C.P. Page
- Publisher
- Elsevier
- Year
- 1995
- Tongue
- English
- Weight
- 360 KB
- Volume
- 8
- Category
- Article
- ISSN
- 0952-0600
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✦ Synopsis
SUMMARY: 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 \mathrm{~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 \mathrm{mg} / \mathrm{kg})), the PDE III inhibitor, milrinone ( (\left.15 \mathrm{mg} / \mathrm{kg}\right)) and the non-selective PDE inhibitor, trequinsin ( (1 \mathrm{mg} / \mathrm{kg}) ) had no effect on eosinophil number or EPO levels. The PDE IV inhibitor, rolipram ((15 \mathrm{mg} / \mathrm{kg})), the mixed type III/IV PDE inhibitor, benzafentrine ((15 \mathrm{mg} / \mathrm{kg})) and the nonselective PDE inhibitor, aminophylline ( (31.5 \mathrm{mg} / \mathrm{kg}) ) had no effect on eosinophil number but reduced the amount of EPO detected. The anti-inflammatory glucocorticosteroids, beclomethasone ((10 \mathrm{mg} / \mathrm{kg})) and betamethasone ((4 \mathrm{mg} / \mathrm{kg})) and the type IV PDE inhibitor, RP (73401(5 \mathrm{mg} / \mathrm{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.