糖皮质激素抵抗型哮喘的临床、糖皮质激素受体及细胞因子特征

目的探讨糖皮质激素抵抗（ＳＲ）型哮喘的临床特征及发生机制。方法选择ＳＲ型哮喘患者１５例及糖皮质激素敏感（ＳＳ）型哮喘患者１５例，比较两型患者的一般临床资料和基础肺功能。采用放射配基结合位点分析法检测外周血单个核细胞（ＰＢＭＣ）的糖皮质激素受体（ＧＣＲ）水平，观察氟美松（１０－７ｍｏｌ／Ｌ）对ＰＢＭＣ产生白细胞介素（ＩＬ）－４的抑制作用。结果除了对泼尼松治疗的临床反应明显不同外，ＳＲ型与ＳＳ型哮喘在一般临床特征及基础肺功能方面差异均无显著性。ＳＲ型哮喘患者ＰＢＭＣ的ＧＣＲ水平显著低于ＳＳ型哮喘患者（Ｐ＜０．０５）。氟美松对ＰＢＭＣ产生ＩＬ－４的抑制作用在ＳＲ型哮喘显著低于ＳＳ型哮喘（Ｐ＜０．００１）。结论对糖皮质激素治疗的反应性差是ＳＲ型哮喘的惟一临床特征。Ｔ细胞对糖皮质激素的抑制作用相对不敏感是ＳＲ型哮喘的细胞学基础，ＧＣＲ异常可能是其原因之一

Steroid resistant asthma: clinical characteristics and abnormality in glucocorticoid receptor and cytokine

Objective To investigate the clinical characteristics and the pathogenesis of steroi dresistant (SR) asthma. Methods 15 patients with SR asthma were studied and 15 patients with steroid sensitive (SS) asthma served as controls. Clinical data and baseline pulmonary function were compared between the two groups. Glucocorticoid receptors (GCR) in peripheral blood mononuclear cells (PBMC) were measured by using radioligand binding assay, and the dexamethasone (10 -7 mol/L) inhibition of IL 4 production by PBMC was evaluated. Results There was no significant difference between SR and SS asthma both in clinical characteristics and baseline pulmonary function, but the response to prednisone therapy was different. Number of GCR in PBMC from SR asthmatics was significantly less than that from SS asthmatics ( P <0.05). Dexamethasone inhibited IL 4 production by PBMC to a much greater degree in SS asthmatics than in SR asthmatics ( P <0.001). Conclusion The results indicate that a poor response to glucocorticoid therapy is the only clinical characteristic of SR asthma. The relative insensitivity of T cells to inhibition by glucocorticoids was the cellular mechanism for SR asthma, which in part may be due to GCR abnormality.