Selective Phosphodiesterase Type 4 Inhibitors Reduce the Prolonged Survival of Eosinophils Stimulated by Granulocyte-Macrophage Colony-Stimulating Factor

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It is well known that bronchial asthma is defined as chronic eosinophilic inflammation of the respiratory tract and that as one of the various types of inflammatory cells, eosinophils induce the airway inflammation of chronic asthma. Granulocyte-maerophage colony-stimulating factor(GM-CSF)has been shown to play an important role in the prolongation or the survival of eosinophis. We investigated the inhibitory effect of the selective phosphodiesterase(PDE)4 inhibitors, 3, 4-dipropyl-4, 5, 7, 8-tetrahydro-3H-imidazo[l, 2-i]purin-5-one(XT611)and rolipram, and the nonselective POE inhibitor theophylline, against GM-CSF-induced prolongation of the survival or eosinophils isolated from patients with bronchial asthma. Eosinophils(10^6cells/ml) were incubated in the presence of GM-CSF together with or without theophylline, rolipram or XT-611 at 37℃, and the viable cells were assessed up to 4d using Trypan blue dye exclusion. The prcsence of theophylline(lO^<-4>M), rolipram(10^<-4>-lO^<-5>M)or XT-611(10^<-4>-10^<-5>M)significantly reduced the GM-CSF(10pg/ml)-induced prolongation of viability of eosinophils. These findings suggest that selective PDE 4 inhibitors, including XT-611, may effectively reduce the activities of in flammatory cells in the airway of bronchial asthma patients.
公益社団法人日本薬学会の論文
2002-02-01