Chakir Jamila, Shannon Joanne, Molet Sophie, Fukakusa Motonori, Elias Jack, Laviolette Michel, Boulet Louis-Philippe, Hamid Qutayba
Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie, Laval, Quebec, Canada.
J Allergy Clin Immunol. 2003 Jun;111(6):1293-8. doi: 10.1067/mai.2003.1557.
Important features of airway remodeling in asthma include the formation of subepithelial fibrosis and increased deposition of types I and III collagen. TGF-beta, 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.
The purpose of this study was to investigate the effect of corticosteroids on the expression of these profibrotic cytokines and on extracellular matrix deposition.
We used immunocytochemistry to measure the expression of TGF-beta, 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.
TGF-beta 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.
These results confirm the association of increased levels of TGF-beta, 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 persistently elevated TGF-beta expression.
哮喘气道重塑的重要特征包括上皮下纤维化的形成以及I型和III型胶原蛋白沉积增加。转化生长因子-β（TGF-β）、白细胞介素-11（IL-11）和白细胞介素-17是参与上皮下纤维化形成的促纤维化细胞因子，在哮喘患者中升高，尤其是重症患者。
本研究旨在探讨皮质类固醇对这些促纤维化细胞因子表达及细胞外基质沉积的影响。
我们采用免疫细胞化学法检测轻度哮喘患者（n = 9）、中重度哮喘患者（n = 10）和无哮喘对照者（n = 6）气道中TGF-β、IL-11、IL-17以及I型和III型胶原蛋白的表达。所有组均获取基线支气管活检标本。此外，中重度哮喘患者在接受为期2周的口服皮质类固醇治疗后进行重复活检。
所有哮喘组中TGF-β表达均显著更高，口服皮质类固醇治疗后并未降低。与轻度哮喘患者和正常对照相比，中重度哮喘患者的IL-11和IL-17水平升高（P <.05）。在中重度组中，这些细胞因子的表达随口服皮质类固醇治疗而降低至与轻度哮喘患者和正常对照相当的水平（P <.005）。中重度哮喘患者I型和III型胶原蛋白的表达高于轻度哮喘患者和对照（P <.05；P <.001）。皮质类固醇治疗并未降低I型和III型胶原蛋白的表达。
这些结果证实TGF-β、IL-11、IL-17以及I型和III型胶原蛋白水平升高与重症疾病相关，并提示皮质类固醇未能降低胶原蛋白沉积可能是由于TGF-β表达持续升高所致。
