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

• Published in: Clinical and experimental allergy Vol. 36; no. 11; pp. 1417 - 1424
• Main Authors: Kawayama, T., O'Byrne, P. M., Watson, R. M., Killian, K. J., Duong, M., Yoshida, M., Gauvreau, G. M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2006; Blackwell
• Subjects: Administration, Inhalation; Adult; airway inflammation; allergen challenge; Allergens; Allergic diseases; Analysis of Variance; Asthma - drug therapy; Asthma - immunology; atopic asthma; Biological and medical sciences; Biomarkers - analysis; Bronchial Provocation Tests; CD4+ lymphocytes; CD4-Positive T-Lymphocytes - immunology; CD8+ lymphocytes; CD8-Positive T-Lymphocytes - immunology; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Eosinophils - immunology; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glucocorticoids - administration & dosage; Glucocorticoids - therapeutic use; Humans; Hypersensitivity - drug therapy; Hypersensitivity - immunology; Immunopathology; Interferon-gamma - analysis; interferon-γ; interleukin-4; Interleukin-4 - analysis; intracellular cytokines; Lymphocyte Count; Male; Medical sciences; Methacholine Chloride; Pregnenediones - administration & dosage; Pregnenediones - therapeutic use; Sputum - immunology; airway inflammation; interleukin-4; Allergy; atopic asthma; interferon-γ; Th1 lymphocyte; Helper cell; Respiratory system; Atopy; Respiratory tract; Interleukin 4; Immunology; T-Lymphocyte; Bronchus disease; Th2 lymphocyte; Obstructive pulmonary disease; Corticosteroid; Immunopathology; Lung disease; CD4+ lymphocytes; intracellular cytokines; Respiratory disease; Cytokine; Inflammation; allergen challenge; Asthma; Inhalation; CD8+ lymphocytes; Intracellular; Ciclesonide; Gamma interferon; Provocation test
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2006.02592.x

Summary 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‐γ (IFN‐γ) 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 μg 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 μg significantly attenuated the late response and sputum eosinophils at 8 h post‐allergen (P<0.05). Circulating IFN‐γ positive CD4+ lymphocytes decreased after allergen challenge with placebo (P<0.05), and this was inhibited by 40 μg ciclesonide treatment (P<0.05). There was no effect of allergen inhalation or ciclesonide on IL‐4‐positive CD4+ lymphocytes or IFN‐γ and IL‐4‐positive CD8high lymphocytes. The allergen‐induced change of IFN‐γ/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‐γ‐positive CD4+ cells.