ACUTE VERSUS CHRONIC ADMINISTRATION OF PHOSPHODIESTERASE INHIBITORS ON ALLERGEN-INDUCED PULMONARY CELL INFLUX IN SENSITIZED GUINEA-PIGS

1 The aims of this study were to determine which phosphodiesterase (PDE) isoenzymes are involved in the control of eosinophil accumulation in the airways of ovalbumin (OVA)-immunized guinea-pigs by the use of isoenzyme selective inhibitors and to compare the effects of acute versus chronic administration of PDE isozyme inhibitors on pulmonary cell influx in ovalbumin-immunized guinea-pigs. 2 Guinea-pigs were sensitized and subsequently challenged with aerosolized OVA. Twenty four hours later bronchoalveolar lavage (BAL) was performed to permit assessment of inflammatory cell accumulation. A significant increase in the number of eosinophils was observed in the lavage fluid from OVA-immunized (13.6 +/- 1.4 x 10(4) ml(-1) in acute experiments and 10.1 +/- 1.4 x 10(4) ml(-1) in chronic experiments) animals compared with sham-treated controls (5.6 +/- 0.6 x 10(4) ml(-)1 in acute experiments and 5.1 +/- 0.6 x 10(4) ml(-1) in chronic experiments). There was no difference in neutrophil, mononuclear cell or total cell numbers between the two groups. 3 Acute administration of a high dose of selective and non-selective PDE inhibitors by the i.p, route had no significant effect on eosinophil accumulation in the airways. 4 Chronic administration of a low dose (3 mg kg(-1), i.p., twice daily for 7 days) of the type IV PDE inhibitor, RO 20-1724, and the PDE III/IV inhibitor, zardaverine, produced a significant inhibition of eosinophil accumulation (46% and 59% respectively). 5 These results suggest that the type IV PDE isoenzyme prays a role in the control of allergen-induced eosinophil infiltration into the airways, but indicate that a period of low dose chronic treatment with a type IV or mixed type III/IV PDE inhibitor is necessary for eosinophil accumulation in the airways to be reduced.