Effects of inhaled ciclesonide on circulating T-helper type 1/T-helper type 2 cells in atopic asthmatics after allergen challenge
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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.
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