Am. J. Respir. Crit. Care Med., Vol 151, No. 6, Jun 1995, 1720-1724.
Modulation of cytokine-induced eosinophil infiltration by phosphodiesterase inhibitors
V Lagente, MP Pruniaux, JL Junien and I Moodley
Laboratoire de Pharmacodynamie, Faculte des Sciences Pharmaceutiques et Biologiques, Universite de Rennes I, France.
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.
