title: IL-5 production by CD4+ T cells of asthmatic patients is suppressed by glucocorticoids and the immunosuppressants FK506 and cyclosporin A.
abstract: IL-5 was produced in vitro by peripheral blood mononuclear cells (PBMC) of mite-sensitive atopic patients upon challenge with specific allergen, while PBMC of healthy controls produced essentially no IL-5. Stimuli delivered by the combination of phorbol ester and Ca2+ ionophore induced marked IL-5 production by PBMC obtained from atopic and non-atopic asthmatics, suggesting that both protein kinase C and Ca2+ influx are required for IL-5 production. CD2- or CD4-bearing cell depletion almost completely removed IL-5-producing cells while CD8-bearing cell depletion rather enriched them. These findings indicate that CD4+ T cells are the principal source of IL-5 in PBMC. The capacity of PBMC of atopic asthmatics, non-atopic asthmatics and healthy controls to produce IL-2, IL-4, IL-5 and IFN-gamma was compared, to find that cytokine-producing capacities other than that of IL-5 (IL-2, IL-4 and IFN-gamma) were not significantly different among the three groups. Dexamethasone, FK506 and cyclosporin A suppressed IL-5 production in vitro in a dose-dependent manner. Clear dose-dependent suppression of IL-5 gene expression by FK506 was also observed. Treatment of asthmatic patients with inhaled glucocorticoid (beclomethasone dipropionate) ameliorated clinical symptoms, improved lung function and markedly suppressed IL-5 production by PBMC, suggesting the essential role of IL-5 in the pathogenesis of bronchial asthma and the clinical importance of its regulation.
authors.affiliation: Department of Medicine and Physical Therapy, University of Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Suko
authors.forename: Y
authors.initials: Y
authors.lastname: Nishizaki
authors.forename: O
authors.initials: O
authors.lastname: Kaminuma
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: G
authors.initials: G
authors.lastname: Matsuzaki
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.forename: N
authors.initials: N
authors.lastname: Tsuruoka
authors.forename: H
authors.initials: H
authors.lastname: Okudaira
mesh_terms: D000328:Adult; D000818:Animals; D039741:Antigens, Dermatophagoides; D001249:Asthma / Q000188:drug therapy / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D001483:Base Sequence; D001507:Beclomethasone / Q000494:pharmacology / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology*; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000235:genetics; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D008925:Mites / Q000276:immunology; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000502:physiology; D015398:Signal Transduction; D016559:Tacrolimus / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D039741:Antigens, Dermatophagoides; D005938:Glucocorticoids; D006023:Glycoproteins; D007376:Interleukin-2; D015848:Interleukin-5; D015847:Interleukin-4; D015759:Ionomycin; D003907:Dexamethasone; D007371:Interferon-gamma; D016572:Cyclosporine; D011493:Protein Kinase C; D001507:Beclomethasone; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D016559:Tacrolimus