Interactive effects of steroids and β-agonists on accumulation of type 2 T cells - 15/08/11
Reprint requests: Raymond B. Penn, PhD, Center for Human Genomics, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157.Abstract |
Background |
Airway inflammation associated with asthma has been reported to be either unaffected or slightly increased by inhaled β-agonist monotherapy, and concerns regarding disease exacerbations with continuous long-acting β-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 β-agonists increase IL-13–producing (IL-13+) or IFN-γ–producing (IFN-γ+) 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-γ+ 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 β-agonist for the β2-adrenergic receptor. Budesonide at greater than 1 nmol/L reversed the augmenting effects of β-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 β-agonist did not affect, numbers of total and IFN-γ+ T cells in IL-2–stimulated cultures.
Conclusion |
β-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.
Le texte complet de cet article est disponible en PDF.Key words : Human, T cells, β-adrenergic receptor, β-agonist, asthma, IL-13, glucocorticosteroid, steroid, IL-2
Abbreviations used : β2AR, GM, Kd, LABA, PBL, SABA
Plan
| Supported by an Independent Investigator award from AstraZeneca to R.B.P. and by National Institutes of Health grant HL58506 (R.B.P.). M.J.L. is a recipient of American Heart Association Beginning Grant-in-Aid 0665390U. Formoterol and budesonide are components of AstraZeneca’s asthma control medication Symbicort. AstraZeneca was not involved in the design of the experiments, the recruitment of volunteers, data generation, or statistical analysis of data. AstraZeneca approved the manuscript before submission. |
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| Disclosure of potential conflict of interest: S. P. Peters has consulting arrangements with the National Institutes of Health, Adelphi, the American Journal of Respiratory and Critical Care Medicine, AstraZeneca, Discovery, Critical Therapeutics, Genentech, Merck, Novartis, Omnicare, the RAD Foundation, Respiratory Medicine, Respiratory Research, Sanofi-Aventis, and Sepracor; has received grant support from Abaris, AstraZeneca, Altana, Boehringer Ingelheim, Centocor, Genentech, GlaxoSmithKline, MedImmune, Novartis, Pfizer, and Wyeth; and is on the speakers’ bureau for AstraZeneca, Merck, Genentech, Novartis, Practicome, Pri-Med, and the RAD Foundation. The rest of the authors have declared that they have no conflict of interest. |
Vol 121 - N° 3
P. 750.e1-755.e3 - mars 2008 Retour au numéro
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