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Chakir, Jamila; Shannon, Joanne; Molet, Sophie; Fukakusa, Motonori; Elias, Jack; Laviolette, Michel; Boulet, Louis-Philippe; Hamid, Qutayba
Journal of allergy and clinical immunology, 06/2003, Volume: 111, Issue: 6Journal Article
Background: Important features of airway remodeling in asthma include the formation of subepithelial fibrosis and increased deposition of types I and III collagen. TGF-β, IL-11, and IL-17 are profibrotic cytokines involved in the formation of subepithelial fibrosis and are increased in patients with asthma, particularly in those with severe disease. Objective: The purpose of this study was to investigate the effect of corticosteroids on the expression of these profibrotic cytokines and on extracellular matrix deposition. Methods: We used immunocytochemistry to measure the expression of TGF-β, IL-11, IL-17, and collagen types I and III in the airways of patients with mild asthma (n = 9), patients with moderate-to-severe asthma (n = 10), and control subjects without asthma (n = 6). Baseline bronchial biopsy specimens were obtained in all groups. In addition, repeat biopsies were obtained in the patients with moderate-to-severe asthma after a 2-week course of oral corticosteroids. Results: TGF-β expression was significantly higher in all groups with asthma, and it did not decrease after treatment with oral corticosteroids. Levels of IL-11 and IL-17 were increased in patients with moderate-to-severe asthma compared with patients with mild asthma and normal controls (P < .05). The expression of these cytokines decreased with oral corticosteroids in the moderate-to-severe group to levels that were comparable to those seen in the patients with mild asthma and in the normal controls (P < .005). Expression of types I and III collagens was higher in the patients with moderate-to-severe asthma than in the patients with mild asthma and the controls (P < .05; P < .001). Treatment with corticosteroids did not decrease the expression of types I and III collagens. Conclusions: These results confirm the association of increased levels of TGF-β, IL-11, IL-17, and types I and III collagens with severe disease and suggest that the failure of cortico-steroids to decrease collagen deposition might be due to per-sistently elevated TGF-β expression. (J Allergy Clin Immunol 2003;111:1293-8.)
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