The effect of selective phosphodiesterase inhibitors in comparison with other anti-asthma drugs on allergen-induced eosinophilia in guinea-pig airways

Pulm Pharmacol. 1995 Feb;8(1):37-42. doi: 10.1006/pulp.1995.1005.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / pharmacology
  • Allergens / immunology*
  • Animals
  • Anti-Asthmatic Agents / pharmacology*
  • Benzamides / pharmacology
  • Eosinophil Peroxidase
  • Eosinophilia / prevention & control*
  • Guinea Pigs
  • Male
  • Peroxidases / metabolism
  • Phosphodiesterase Inhibitors / pharmacology*
  • Pyridines / pharmacology

Substances

  • Adrenal Cortex Hormones
  • Allergens
  • Anti-Asthmatic Agents
  • Benzamides
  • Phosphodiesterase Inhibitors
  • Pyridines
  • Eosinophil Peroxidase
  • Peroxidases
  • piclamilast