title: Interleukin-10-secreting "regulatory" T cells induced by glucocorticoids and beta2-agonists.
abstract: Greater clinical benefit in controlling the symptoms of asthma is frequently observed through combining moderate doses of inhaled glucocorticoids together with long-acting beta(2)-agonists, as compared with increasing glucocorticoid dosage alone. To address in vitro whether glucocorticoids plus beta(2)-agonists, compared with glucocorticoids alone, have greater inhibitory activity on CD4+ T cell responses to allergen, peripheral blood CD4+ T cell responses to allergen were compared in the presence or absence of the glucocorticoid fluticasone proprionate and the short- and long-acting beta(2)-agonists salbutamol and salmeterol, respectively. Fluticasone proprionate inhibited interleukin (IL)-5 and IL-13 and enhanced IL-10 synthesis in allergen-stimulated cultures in a concentration-dependent manner. Salmeterol, but not salbutamol, inhibited IL-5 and IL-13 and enhanced IL-10 synthesis in these cultures. When used in combination the two drugs demonstrated an additive effect on this pattern of cytokine production. Allergen-specific T cell lines induced in the presence of salmeterol and fluticasone proprionate inhibited IL-5 and IL-13 production by allergen-specific Th2 cell lines in an IL-10-dependent manner. Thus fluticasone proprionate and salmeterol increased IL-10 and reduced Th2 cytokine synthesis additively in allergen stimulated human CD4+ T cells.
authors.affiliation: Department of Asthma, Allergy and Respiratory Science, GKT School of Medicine, King's College London, Guy's Hospital, UK.
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Peek
authors.forename: David F
authors.initials: DF
authors.lastname: Richards
authors.forename: Alexander
authors.initials: A
authors.lastname: Faith
authors.forename: Paul
authors.initials: P
authors.lastname: Lavender
authors.forename: Tak H
authors.initials: TH
authors.lastname: Lee
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Corrigan
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Hawrylowicz
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000485:Allergens / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D000068298:Fluticasone; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D018793:Interleukin-13 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000068299:Salmeterol Xinafoate; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D000485:Allergens; D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005938:Glucocorticoids; D018793:Interleukin-13; D015848:Interleukin-5; D016753:Interleukin-10; D000068299:Salmeterol Xinafoate; D007371:Interferon-gamma; D000068298:Fluticasone; D000420:Albuterol