The antiallergic drug oxatomide promotes human eosinophil apoptosis and suppresses IL-5-induced eosinophil survival

Background: Eosinophils accumulated in sites of allergic inflammation are thought to play a crucial role in the pathogenesis of allergic disorders including asthma, allergic rhinitis, and atopic dermatitis, and tissue eosinophilia is attributable to increased eosinophil survival or decreased eosinophil Apoptosis.

Objective: Effects of the antiallergic, histamine H1 blocker oxatomide on viability and Apoptosis of eosinophils isolated from the peripheral blood of atopic subjects were studied.

Methods: Eosinophil viability and Apoptosis were evaluated by using a colorimetric assay and annexin V-labeling, Caspase-3 activity, and DNA fragmentation assay.

Results: The viability of eosinophils increased in the presence of IL-5 (10 ng/mL), confirming that IL-5 prolongs eosinophil survival in vitro. Application of oxatomide at concentrations over 20 micromol/L for 24 hours decreased the IL-5-induced enhancement of eosinophil viability. Double staining of the cells with annexin V and propidium iodide showed that deprivation of IL-5 promoted spontaneous eosinophil Apoptosis and that oxatomide facilitated Apoptosis and suppressed the prolongation of eosinophil survival stimulated by IL-5. In the absence of IL-5, approximately 71% and 96% of eosinophils after 24 and 48 hours, respectively, underwent spontaneous Apoptosis. IL-5 decreased the rate of eosinophil Apoptosis to 38% and 52% after 24 and 48 hours, respectively. Oxatomide increased eosinophil Apoptosis in a concentration-dependent manner in the presence of IL-5. Furthermore, oxatomide increased Caspase-3 activity and DNA fragmentation.

Conclusion: We demonstrated that oxatomide possesses a novel therapeutic effect of Apoptosis promotion on eosinophils and prevents the antiapoptotic effects of IL-5, suggesting that oxatomide may contribute to resolution of tissue eosinophilia in allergic inflammation.