MODULATION OF CYTOKINE-INDUCED EOSINOPHIL INFILTRATION BY PHOSPHODIESTERASE INHIBITORS

The effects of selective phosphodiesterase (PDE) isoenzyme inhibitors on eosinophil airway infiltration induced by intratracheal administrat ion of recombinant human cytokines were investigated in the guinea pig . Recombinant human IL-5 and IL-8 elicited a concentration-dependent i ncrease in the number of eosinophils in the bronchoalveolar lavage (BA L) fluid. In contrast, no effect was observed after intratracheal inje ction of recombinant human IL-3 or recombinant human RANTES. Pretreatm ent with the PDE IV inhibitors rolipram or Ro 20-1724 or the nonselect ive PDE inhibitor theophylline 1 h before intratracheal injection of I L-5 significantly reduced the number of eosinophils in the BAL fluid a t 48 h. In contrast, the selective PDE Ill inhibitors milrinone and SK andF 94-836 and the PDE IN inhibitor zaprinast did not inhibit the air way eosinophil infiltration induced by IL-5. Betamethasone also signif icantly inhibited the IL-5-induced eosinophil infiltration in BAL flui d. Administration of rolipram or betamethasone 1 h before IL-8 signifi cantly reduced airway eosinophil infiltration. Because the selective P DE IV inhibitors markedly inhibited eosinophil infiltration in guinea pig airways induced by cytokines, it is suggested that PDE IV inhibito rs have antiinflammatory effects in the airways and may be useful in t he treatment of asthma.