BACKGROUND: Airway inflammation associated with asthma has been reported to be either unaffected or slightly increased by inhaled beta-agonist monotherapy, and concerns regarding disease exacerbations with continuous long-acting beta-agonist monotherapy have prompted the recommendation of concomitant steroid treatment. OBJECTIVES: Using peripheral blood lymphocytes from asthmatic subjects, we aimed to determine (1) whether short- or long-acting beta-agonists increase IL-13-producing (IL-13+ or IFN-gamma-producing (IFN-gamma+ T-cell numbers and (2) the ability of the corticosteroid budesonide to reverse these effects. METHODS: Peripheral blood lymphocytes from asthmatic subjects were cultured 6 days ex vivo with IL-2 and various concentrations of albuterol, formoterol, and budesonide. Numbers of IL-13+ and IFN-gamma+ T cells were determined by means of flow cytometric analysis. RESULTS: Both albuterol and formoterol increased IL-2-stimulated accumulation of IL-13+ T cells, and this increase was highest at concentrations approximating the dissociation constant of each beta-agonist for the beta(2)-adrenergic receptor. Budesonide at greater than 1 nmol/L reversed the augmenting effects of beta-agonists on IL-13+ T-cell accumulation, and budesonide at greater than 10 nmol/L inhibited increases in IL-13+ T cells stimulated by IL-2. Budesonide decreased, whereas beta-agonist did not affect, numbers of total and IFN-gamma+ T cells in IL-2-stimulated cultures. CONCLUSION: beta-Agonists at physiologically and clinically relevant concentrations stimulate increased antigen-independent, cytokine-stimulated accumulation, specifically of type 2 T cells from asthmatic subjects. The corticosteroid budesonide potently reverses this effect.
BACKGROUND: Airway inflammation associated with asthma has been reported to be either unaffected or slightly increased by inhaled beta-agonist monotherapy, and concerns regarding disease exacerbations with continuous long-acting beta-agonist monotherapy have prompted the recommendation of concomitant steroid treatment. OBJECTIVES: Using peripheral blood lymphocytes from asthmatic subjects, we aimed to determine (1) whether short- or long-acting beta-agonists increase IL-13-producing (IL-13+ or IFN-gamma-producing (IFN-gamma+ T-cell numbers and (2) the ability of the corticosteroid budesonide to reverse these effects. METHODS: Peripheral blood lymphocytes from asthmatic subjects were cultured 6 days ex vivo with IL-2 and various concentrations of albuterol, formoterol, and budesonide. Numbers of IL-13+ and IFN-gamma+ T cells were determined by means of flow cytometric analysis. RESULTS: Both albuterol and formoterol increased IL-2-stimulated accumulation of IL-13+ T cells, and this increase was highest at concentrations approximating the dissociation constant of each beta-agonist for the beta(2)-adrenergic receptor. Budesonide at greater than 1 nmol/L reversed the augmenting effects of beta-agonists on IL-13+ T-cell accumulation, and budesonide at greater than 10 nmol/L inhibited increases in IL-13+ T cells stimulated by IL-2. Budesonide decreased, whereas beta-agonist did not affect, numbers of total and IFN-gamma+ T cells in IL-2-stimulated cultures. CONCLUSION: beta-Agonists at physiologically and clinically relevant concentrations stimulate increased antigen-independent, cytokine-stimulated accumulation, specifically of type 2 T cells from asthmatic subjects. The corticosteroid budesonide potently reverses this effect.
Authors: Rui Lin; Simone Degan; Barbara S Theriot; Bernard M Fischer; Ryan T Strachan; Jiurong Liang; Richard A Pierce; Mary E Sunday; Paul W Noble; Monica Kraft; Arnold R Brody; Julia K L Walker Journal: Br J Pharmacol Date: 2012-04 Impact factor: 8.739
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Authors: Anna G Taranova; David Maldonado; Celine M Vachon; Elizabeth A Jacobsen; Hiam Abdala-Valencia; Michael P McGarry; Sergei I Ochkur; Cheryl A Protheroe; Alfred Doyle; Clive S Grant; Joan Cook-Mills; Lutz Birnbaumer; Nancy A Lee; James J Lee Journal: Cancer Res Date: 2008-10-15 Impact factor: 12.701
Authors: Lennart K A Lundblad; Lisa M Rinaldi; Matthew E Poynter; Erik P Riesenfeld; Min Wu; Steven Aimi; Leesa M Barone; Jason H T Bates; Charles G Irvin Journal: Respir Res Date: 2011-03-07