The effects of selective
phosphodiesterase (PDE)
isoenzyme inhibitors on eosinophil airway infiltration induced by intratracheal administration of recombinant human
cytokines were investigated in the guinea pig. Recombinant human
IL-5 and
IL-8 elicited a concentration-dependent increase in the number of eosinophils in the bronchoalveolar lavage (BAL) fluid. In contrast, no effect was observed after intratracheal injection of recombinant human
IL-3 or recombinant human
RANTES. Pretreatment with the PDE IV inhibitors
rolipram or
Ro 20-1724 or the nonselective PDE inhibitor
theophylline 1 h before intratracheal injection of
IL-5 significantly reduced the number of eosinophils in the BAL fluid at 48 h. In contrast, the selective PDE III inhibitors
milrinone and SK&F 94-836 and the PDE I/V inhibitor
zaprinast did not inhibit the airway eosinophil infiltration induced by
IL-5.
Betamethasone also significantly inhibited the IL-5-induced eosinophil infiltration in BAL fluid. Administration of
rolipram or
betamethasone 1 h before
IL-8 significantly reduced airway eosinophil infiltration. Because the selective PDE IV inhibitors markedly inhibited eosinophil infiltration in guinea pig airways induced by
cytokines, it is suggested that PDE IV inhibitors have antiinflammatory effects in the airways and may be useful in the treatment of
asthma.