糖皮质激素抵抗型哮喘的免疫学研究

Immunological features of steroid resistant asthma

目的探讨糖皮质激素抵抗型（ＳＲ）哮喘的发生机制及治疗对策。方法检测ＳＲ哮喘及糖皮质激素敏感性（ＳＳ），哮喘患者经强的松（２０ｍｇ／ｄ）治疗前后血清可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）水平的变化，用体外淋巴细胞增殖试验观察地塞米松、氧化苦参碱和胸腺免疫抑制物对外周血Ｔ细胞增殖的抑制作用。结果强的松治疗后，ＳＳ哮喘患者的血清ｓＩＬ－２Ｒ水平显著降低（Ｐ＜０．００１），但ＳＲ哮喘患者的ｓＩＬ－２Ｒ水平无明显变化（Ｐ＞０．５）。地塞米松（１０－７ｍｏｌ／Ｌ）对ＳＲ哮喘患者Ｔ细胞增殖的抑制作用显著低于ＳＳ哮喘患者（Ｐ＜０．００２），但氧化苦参碱和胸腺免疫抑制物对Ｔ细胞增殖的抑制作用在两组患者之间差异无显著性。结论Ｔ细胞对糖皮质激素的反应性降低以及由此引起的Ｔ细胞持续活化是ＳＲ哮喘的免疫学特征。糖皮质激素以外的免疫抑制剂在ＳＲ哮喘治疗中的意义值得进一步探讨。

Objective To investigate the pathogenesis and treatment of steroid resistant (SR) asthma. Methods Changes of serum levels of soluble interleukin 2 receptor (sIL 2R) after oral prednisone (20mg/d) therapy were observed, and the peripheral blood T cell inhibitory effects of dexamethasone, oxymatrine and thymus derived immunoinhibiting agents were studied in vitro by lymphocyte proliferation assay. Results After prednisone therapy, serum levels of sIL 2R were significantly decreased in steroid sensitive (SS) asthmatics ( P <0.001) but not in SR asthmatics ( P >0.5). The inhibitory effects of dexamethasone (10 -7 mol/L) on the proliferation of T cells from SR asthmatics were significantly less than those from SS asthmatics ( P <0.002). Oxymatrine and thymus derived immuno inhibiting agents inhibited T cell proliferation to a similar degree between SR and SS asthmatics. Conclusions Persistent T cell activation due to relative unresponsiveness of T cells to glucocorticoids was a feature of SR asthma. The therapeutic benefit of immuno inhibiting agents other than glucocorticoids in the management of SR asthma deserves further investigation.