title: Cyclic AMP-elevating agents inhibit mite-antigen-induced IL-4 and IL-13 release from basophil-enriched leukocyte preparation.
abstract: Human peripheral blood basophils are known to secrete interleukin (IL)-4 and IL-13 after cross-linking of cell surface IgE. However, little is known about the pharmacological regulation of allergic cytokine release from basophils. In the present study, we investigated the effects of cyclic 3',5'-adenosine monophosphate (cAMP)-elevating agents on antigen-induced IL-4 and IL-13 release from basophil-enriched leukocyte preparations. We obtained venous blood from 27 atopic asthmatic patients (mean age was 45.8+/-3.6 years, all patients were sensitive to mite antigen) and prepared basophil-enriched leukocyte preparations by double-Percoll gradients (basophil purity was 13.4+/-1.6%). The cell preparations were treated with phosphodiesterase (PDE) inhibitors, dexamethasone, forskolin or dibutyryl cAMP for 10 min and were challenged with mite antigen for 6 h. The released IL-4 and IL-13 in the supernatants were measured by enzyme-linked immunosorbent assay systems. No IL-4 or IL-13 was detected in the supernatant of the basophil-depleted preparation after the challenge with mite antigen, suggesting that basophils specifically produce these cytokines. A nonselective PDE inhibitor, theophylline, and a PDE IV-selective inhibitor, rolipram, significantly suppressed the release of IL-4 and IL-13 from the basophil-enriched preparation. Although several concentrations of cilostazol, a PDE III-selective inhibitor, had no effect on the release of both cytokines, cilostazol suppressed the release of IL-4 additively when applied with rolipram. Forskolin and dibutyril cAMP also significantly suppressed the release of both cytokines, suggesting that the suppressive effects by PDE inhibitors were accompanied by the elevations in cAMP levels. We conclude that basophil-enriched leukocyte preparations produce IL-4 and IL-13 in response to antigen and that the release of these cytokines could be regulated by cAMP-modulating agents.
authors.affiliation: Department of Pharmacology, Gifu Pharmaceutical University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shichijo
authors.forename: Y
authors.initials: Y
authors.lastname: Shimizu
authors.forename: K
authors.initials: K
authors.lastname: Hiramatsu
authors.forename: N
authors.initials: N
authors.lastname: Inagaki
authors.forename: K
authors.initials: K
authors.lastname: Tagaki
authors.forename: H
authors.initials: H
authors.lastname: Nagai
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D001491:Basophils / Q000187:drug effects / Q000276:immunology*; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D008925:Mites / Q000276:immunology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology
chemical_list: D000941:Antigens; D018793:Interleukin-13; D007378:Interleukins; D010726:Phosphodiesterase Inhibitors; D005576:Colforsin; D015847:Interleukin-4; D003994:Bucladesine; D003907:Dexamethasone; D000242:Cyclic AMP