Modulation of cytokine-induced eosinophil infiltration by phosphodiesterase inhibitors.
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.
Lagente
V
V
Laboratoire de Pharmacodynamie, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes I, France.
Pruniaux
M P
MP
Junien
J L
JL
Moodley
I
I
D000818:Animals; D001249:Asthma / Q000188:drug therapy; D001623:Betamethasone / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018946:Chemokine CCL5; D016207:Cytokines / Q000494:pharmacology*; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D007377:Interleukin-3 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011292:Premedication; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D014132:Trachea / Q000187:drug effects
D018946:Chemokine CCL5; D016207:Cytokines; D007377:Interleukin-3; D015848:Interleukin-5; D016209:Interleukin-8; D008222:Lymphokines; D010726:Phosphodiesterase Inhibitors; D011994:Recombinant Proteins; D001623:Betamethasone