Kinetics of allergen-induced airway eosinophilic cytokine production and airway inflammation.
Airway eosinophilia is the hallmark of asthma exacerbation. Coordination of cytokines such as interleukin (IL)-5, eotaxin and regulated on activation, normal T-cell expressed and secreted (RANTES) seem to be necessary for eosinophil extravasation including adhesion, chemotaxis, and activation. The purpose of this study was to characterize both the kinetics of allergen-induced inflammatory cell recruitment to the airways and cytokines selective for eosinophil chemotaxis, activation, or resolution. Eight atopic asthmatic individuals demonstrating a dual response to inhaled allergen completed a diluent-controlled crossover study. The subjects showed significant allergen-induced early and late airway asthmatic responses (p < 0.001), and an increase in the number of sputum eosinophils and metachromatic cells (p < 0.05). The number of eosinophils immunopositive for IL-5, eotaxin, and RANTES increased 7 h after allergen inhalation (p < 0.05), coincident with the peak number of activated eosinophils. Sputum cells immunopositive for IL-10 decreased significantly following allergen challenge (p = 0. 04), and correlated negatively with sputum eosinophils (r = -0.34, p = 0.02). This study shows that allergen-induced increases in sputum eosinophils are associated with the presence of cytokines specific for the activation and chemotaxis of eosinophils, and suggests that cooperation of eosinophilic cytokines may be important for the accumulation and regulation of activated eosinophils at the site of allergic inflammation.
Gauvreau
G M
GM
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Watson
R M
RM
O'Byrne
P M
PM
D000328:Adult; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D001980:Bronchi / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001985:Bronchial Provocation Tests; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000378:metabolism; D019742:Chemokines, CC; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D004802:Eosinophilia / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D015848:Interleukin-5 / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D013183:Sputum / Q000166:cytology
D000485:Allergens; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D016207:Cytokines; D015848:Interleukin-5