Fluticasone induces T cell apoptosis in the bronchial wall of mild to moderate asthmatics.
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 microg twice daily) for 2 weeks could modulate production of IL-15 or IFN-beta 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-beta 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-beta 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).


CONCLUSIONS
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.
O'Sullivan
S
S
Department of Immunology, Royal Free and University College Hospital Medical School, London NW3 2QG, UK. sioosu@indigo.ie
Cormican
L
L
Burke
C M
CM
Poulter
L W
LW
D000280:Administration, Inhalation; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology; D001706:Biopsy / Q000379:methods; D001980:Bronchi / Q000473:pathology*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D015536:Down-Regulation; D005260:Female; D000068298:Fluticasone; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D008297:Male; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology
D000730:Androstadienes; D001993:Bronchodilator Agents; D019409:Interleukin-15; D016899:Interferon-beta; D000068298:Fluticasone