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

• Published in: Thorax Vol. 59; no. 8; pp. 657 - 661
• Main Authors: O’Sullivan, S, Cormican, L, Burke, C M, Poulter, L W
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Thoracic Society 01.08.2004; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Administration, Inhalation; Adult; Allergens; Androstadienes - administration & dosage; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Apoptosis; Apoptosis - drug effects; Asthma; Asthma - drug therapy; Asthma - pathology; Biological and medical sciences; Biopsy; Biopsy - methods; Bronchi - pathology; Bronchodilator Agents - administration & dosage; Bronchoscopy; Cardiology. Vascular system; Cell death; Chronic obstructive pulmonary disease, asthma; Cytokines; Down-Regulation; Female; Fluticasone; fluticasone propionate; Humans; Inflammation; Interferon-beta - metabolism; Interleukin-15 - metabolism; Ligands; Lymphocytes; Male; Medical sciences; Pneumology; Steroids; T cells; T-Lymphocytes - drug effects; T-Lymphocytes - physiology; United Kingdom > UK; Lung disease; Wall; Respiratory disease; Fluticasone; Respiratory system; Asthma; Respiratory tract; T-Lymphocyte; Bronchus disease; Anesthesia; Obstructive pulmonary disease; Circulatory system; Cardiology; Apoptosis
• ISSN: 0040-6376; 1468-3296
• DOI: 10.1136/thx.2002.001586

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.