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 (PD E) isoenzymes are involved in the control of eosinophil accumulation i n the airways of ovalbumin (OVA)-immunized guinea-pigs by the use of i soenzyme selective inhibitors and to compare the effects of acute vers us chronic administration of PDE isozyme inhibitors on pulmonary cell influx in ovalbumin-immunized guinea-pigs. 2 Guinea-pigs were sensitiz ed 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 numb er 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 1 0(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 i n neutrophil, mononuclear cell or total cell numbers between the two g roups. 3 Acute administration of a high dose of selective and non-sele ctive PDE inhibitors by the i.p, route had no significant effect on eo sinophil accumulation in the airways. 4 Chronic administration of a lo w 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, prod uced 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 infiltratio n into the airways, but indicate that a period of low dose chronic tre atment with a type IV or mixed type III/IV PDE inhibitor is necessary for eosinophil accumulation in the airways to be reduced.