Effects of inhaled fluticasone propionate on CTLA-4-positive CD4+CD25+ cells in induced sputum in mild asthmatics.
OBJECTIVE
Cytotoxic T-lymphocyte antigen 4 (CTLA-4) signalling of regulatory T cells regulates mucosal lymphocyte tolerance and differentiation, and may therefore have a beneficial effect in allergic diseases such as asthma. The aim of this study was to evaluate the effects of fluticasone propionate (FP) on CD4+CD25+ T cell co-expression of CTLA-4 in the sputum of mild asthmatic subjects.


METHODS
Eleven mild, stable asthmatic subjects completed a double-blind, randomized, crossover, placebo-controlled study to compare the effects of 14 days 200 microg twice daily FP and placebo. Before and after treatment, airway hyperresponsiveness was measured, and sputum was induced for measurements of CTLA-4+CD4+CD25+ cells, eosinophils and levels of IL-10, IL-13 and transforming growth factor (TGF)-beta.


RESULTS
FP treatment increased co-expression of CTLA-4 on sputum CD4+CD25+ cells from a mean (SEM) of 7.9% (1.8) to 12.7% (3.3) after 14 days treatment (P < 0.05) compared with placebo. FP treatment also significantly increased IL-10 levels, reduced per cent sputum eosinophils, and reduced airway hyperresponsiveness (P < 0.05). There was a significant negative correlation between the change in airway hyperresponsiveness and per cent sputum eosinophils (P < 0.01), but no correlation with changes in CTLA-4+CD4+CD25+ cells (P > 0.05). There was no change in the levels of sputum IL-13 or TGF-beta.


CONCLUSIONS
The percentage of airway CTLA-4+CD4+CD25+ cells increased after FP treatment, coincident with improvements in airway inflammation and hyperresponsiveness.Whether improved asthma assessments are related to the increase in CTLA-4+CD4+CD25+ cells and thus improved regulation of T-cell tolerance and differentiation will require a larger sample size to determine. The normalization of CTLA-4+CD4+CD25+ cells in asthma may contribute to the management of this disease.
Kawayama
Tomotaka
T
Department of Medicine, Division of Respirology, Neurology and Rheumatology, Kurume University School of Medicine, Kurume, Japan. kawayama_tomotaka@med.kurume-u.ac.jp
Kinoshita
Takashi
T
Imaoka
Haruki
H
Gauvreau
Gail M
GM
O'Byrne
Paul M
PM
Aizawa
Hisamichi
H
D000280:Administration, Inhalation; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage*; D015703:Antigens, CD / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D060908:CTLA-4 Antigen; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D000068298:Fluticasone; D005500:Follow-Up Studies; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D012720:Severity of Illness Index; D013183:Sputum / Q000737:chemistry* / Q000166:cytology; D055815:Young Adult
D000730:Androstadienes; D015703:Antigens, CD; D001993:Bronchodilator Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D000068298:Fluticasone