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Interleukin-10–Secreting "Regulatory" T Cells Induced by Glucocorticoids and ß₂-Agonists

Department of Asthma, Allergy and Respiratory Science, GKT School of Medicine, King's College London, Guy's Hospital, London, United Kingdom

Correspondence and requests for reprints should be addressed to Dr. Catherine M. Hawrylowicz, Department of Asthma, Allergy and Respiratory Science, 5th Floor Thomas Guy House, GKT School of Medicine, King's College London, Guy's Hospital, London SE1 9RT, UK. E-mail: catherine.hawrylowicz{at}kcl.ac.uk

Greater clinical benefit in controlling the symptoms of asthma is frequently observed through combining moderate doses of inhaled glucocorticoids together with long-acting ß₂-agonists, as compared with increasing glucocorticoid dosage alone. To address in vitro whether glucocorticoids plus ß₂-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 ß₂-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.

Key Words: interleukin-10 • glucocorticoids • ß₂-agonists • regulatory T cells