Effects of inhaled ciclesonide on circulating T-helper type 1/T-helper type 2 cells in atopic asthmatics after allergen challenge.
BACKGROUND
The predominance of T-helper type 2 (Th2) lymphocytes is thought to underlie the pathogenesis of asthma. Allergen inhalation challenge in atopic asthmatic subjects is associated with decreased interferon-gamma (IFN-gamma) positive CD4+ and CD8+ lymphocytes in peripheral blood and induced sputum.


OBJECTIVE
This study examined the effects of an inhaled corticosteroid on these previously described allergen-induced changes in circulating Th1 and Th2 lymphocytes.


METHODS
Subjects were randomized to 7 days of placebo, 40 or 80 micro g ciclesonide in a crossover study. Airway responses and peripheral blood were measured before and after treatment, and 24 h after allergen challenge.


RESULTS
Ciclesonide 40 and 80 micro g significantly attenuated the late response and sputum eosinophils at 8 h post-allergen (P<0.05). Circulating IFN-gamma positive CD4+ lymphocytes decreased after allergen challenge with placebo (P<0.05), and this was inhibited by 40 micro g ciclesonide treatment (P<0.05). There was no effect of allergen inhalation or ciclesonide on IL-4-positive CD4+ lymphocytes or IFN-gamma and IL-4-positive CD8(high) lymphocytes. The allergen-induced change of IFN-gamma/IL-4 ratio on CD4+ cells correlated with the allergen-induced change of peripheral blood eosinophils.


CONCLUSIONS
The results of this study suggest that attenuation of allergen-induced airway responses by ciclesonide may be mediated through regulation of IFN-gamma-positive CD4+ cells.
Kawayama
T
T
First Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
O'Byrne
P M
PM
Watson
R M
RM
Killian
K J
KJ
Duong
M
M
Yoshida
M
M
Gauvreau
G M
GM
D000280:Administration, Inhalation; D000328:Adult; D000485:Allergens; D000704:Analysis of Variance; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D001985:Bronchial Provocation Tests; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004804:Eosinophils / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D018655:Lymphocyte Count; D008297:Male; D016210:Methacholine Chloride; D011282:Pregnenediones / Q000008:administration & dosage* / Q000627:therapeutic use; D013183:Sputum / Q000276:immunology
D000485:Allergens; D015415:Biomarkers; D005938:Glucocorticoids; D011282:Pregnenediones; D016210:Methacholine Chloride; D015847:Interleukin-4; D007371:Interferon-gamma; C120481:ciclesonide