Acute versus chronic administration of phosphodiesterase inhibitors on allergen-induced pulmonary cell influx in sensitized guinea-pigs

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Abstract
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 × 104ml−1 in acute experiments and 10.1 ± 1.4 × 104 ml−1 in chronic experiments) animals compared with sham-treated controls (5.6 ± 0.6 × 104 ml−1 in acute experiments and 5.1 ± 0.6 × 104 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 plays 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.