Interactive effects of steroids and beta-agonists on accumulation of type 2 T cells.
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.


OBJECTIVE
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.


CONCLUSIONS
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.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D001249:Asthma / Q000276:immunology*; D019819:Budesonide / Q000494:pharmacology; D002478:Cells, Cultured; D004983:Ethanolamines / Q000494:pharmacology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D000068759:Formoterol Fumarate; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D018793:Interleukin-13 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology*
D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D018793:Interleukin-13; D007376:Interleukin-2; D019819:Budesonide; D007371:Interferon-gamma; D000420:Albuterol; D000068759:Formoterol Fumarate