Ho C Y, Wong C K, Li E K, Lam W K
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT.
Immunol Invest. 2001 Aug;30(3):231-43. doi: 10.1081/imm-100105067.
Previous studies have shown that the autoimmune phenomenon could be caused by defective apoptosis of autoreactive lymphocytes. Corticosteroids used for treatment of systemic lupus erythematosus (SLE) are potent apoptosis inducers. We examined dexamethasone (DEX)-induced apoptosis and Fas expression in peripheral blood lymphocytes of SLE patients and normal subjects. Peripheral blood lymphocytes were obtained from 40 SLE patients and 18 sex- and age-matched control subjects. Percentages of apoptosis and expression of Fas molecule in lymphocytes were assessed by flow cytometry. Fas expression in lymphocytes treated with or without DEX was significantly higher in SLE patients than normal controls [median (interquartile range) of mean fluorescence intensity without DEX: 74.9 (50.7-98.0) vs 20.0 (17.7-25.0), p < 0.001; with DEX: 77.9 (56.0-130.5) vs 20.5 (18.6-24.7), p<0.001]. DEX (0.1-5 microM) could also induce apoptosis of lymphocytes from SLE and control subjects in a dose-dependent manner. Elevation of apoptotic susceptibility was more prominent in DEX-treated SLE lymphocytes [33.9% (24.7-37.5%) vs 19.6% (13.6-26.1 %), p = 0.003]. The higher apoptotic susceptibility of SLE lymphocytes upon DEX treatment in vitro may be related, at least partly, to the pharmacological action of corticosteroids.
以往研究表明，自身免疫现象可能由自身反应性淋巴细胞凋亡缺陷引起。用于治疗系统性红斑狼疮（SLE）的皮质类固醇是强效凋亡诱导剂。我们检测了地塞米松（DEX）诱导的SLE患者和正常受试者外周血淋巴细胞凋亡及Fas表达情况。从40例SLE患者和18例年龄及性别匹配的对照受试者获取外周血淋巴细胞。通过流式细胞术评估淋巴细胞凋亡百分比及Fas分子表达。无论有无DEX处理，SLE患者淋巴细胞中Fas表达均显著高于正常对照[未用DEX时平均荧光强度的中位数（四分位间距）：74.9（50.7 - 98.0）对20.0（17.7 - 25.0），p < 0.001；用DEX时：77.9（56.0 - 130.5）对20.5（18.6 - 24.7），p < 0.001]。DEX（0.1 - 5 microM）也能以剂量依赖方式诱导SLE患者和对照受试者的淋巴细胞凋亡。DEX处理的SLE淋巴细胞凋亡易感性升高更显著[33.9%（24.7 - 37.5%）对19.6%（13.6 - 26.1%），p = 0.003]。体外DEX处理时SLE淋巴细胞较高的凋亡易感性可能至少部分与皮质类固醇的药理作用有关。
