Fluticasone induces T cell apoptosis in the bronchial wall of mild to moderate asthmatics

Abstract

Background: Cytokines which signal via the gamma chain of the interleukin (IL)-2 receptor and the interferons (IFNs) have been shown to enhance T cell survival in vitro by rescuing cells from apoptosis. Methods: A study was undertaken to determine whether treatment with inhaled fluticasone propionate (FP; 250 μg twice daily) for 2 weeks could modulate production of IL-15 or IFN-β and thereby affect T cell survival in bronchial tissue of 10 patients with mild/moderate asthma. Bronchial biopsy specimens were taken before and on completion of treatment. Results: The mean (95% CI) number of T cells per unit area decreased in the asthmatic group following 2 weeks of treatment with FP (from 7.0 (5.6 to 8.4) to 4.5 (4.0 to 5.1 ); p = 0.001). There was an increase in the percentage of T cells undergoing apoptosis following FP treatment as assessed by T cell/TUNEL staining (from 4.5 (2.6 to 6.4) to 8.7 (6.6 to 10.8); p = 0.0001). The percentage of cells staining for IL-15 and IFN-β in the lamina propria, determined by an alkaline phosphatase biotin streptavidin technique, decreased significantly from baseline values of 31.6 (23.4 to 39.7) to 19.6 (12.5 to 26.7), p = 0.039 for IL-15 and from 18.9 (13.5 to 24.4) to 9.5 (5.9 to 13.1), p = 0.007 for IFN-β following 2 weeks of treatment with FP. However, only the decrease in the percentage of cells staining for IL-15 was significantly correlated with an increased number of apoptotic T cells following treatment (p = 0.008). Conclusion: These findings support a novel mechanism for the ability of inhaled corticosteroids to decrease T cell numbers, possibly by downregulation of the cytokine IL-15.