Role of dehydroepiandrosterone deficiency for the impaired interleukin 2 production of T cells in human systemic lupus erythematosus

IL-2缺乏是鼠狼疮和人系统性红斑狼疮（SLE）的共同特征，其主要原因尚不清楚。我们自己和其他人最近的研究表明，脱氢表雄酮（DHEA），一种睾酮合成的中间化合物，显著上调T细胞IL-2的产生，并且通过痘苗构建的外源性DHEA或IL-2治疗小鼠狼疮显着逆转其临床自身免疫性疾病。因此，我们检测了SLE患者的血清脱氢表雄酮水平，以检测脱氢表雄酮活性异常是否与患者IL-2缺乏有关。我们发现几乎所有接受检查的患者血清脱氢表雄酮水平都很低。脱氢表雄酮水平的下降不仅仅是长期皮质类固醇治疗可能导致肾上腺萎缩的反映，因为在疾病发作时提取的血清样本，没有皮质类固醇治疗，也含有低水平的脱氢表雄酮。此外，在体外实验中，外源性脱氢表雄酮可以恢复SLE患者体内受损的T细胞IL-2生成。这些结果表明，SLE患者IL-2合成缺陷至少部分是由于血清中脱氢表雄酮活性低。

Principal cause of the IL-2 deficiency, a common feature of both murine lupus and human systemic lupus erythematosus(SLE) remain obscure. Recent studies of our own as well as others have shown that dehydroepiandrosterone(DHEA), an intermediate compound in testosterone synthesis, significantly upregulates IL-2 production of T cells and that administration of exogenous DHEA or IL-2 via a vaccinia construct to murine lupus dramatically reverses their clinical autoimmune diseases. Thus, we have examined serum levels of DHEA in patients with SLE to test whether abnormal DHEA activity is associated with the IL-2 deficiency of the patients. We found that nearly all of the patients examined have very low levels of serum DHEA.The decreased DHEA levels are not simply a reflection of a long term corticosteroid treatment which may cause adrenal atrophy, since serum samples drawn at the onset of disease, which are devoid of corticosteroid treatment also contained low levels of DHEA.In addition, exogenous DHEA restored impaired IL-2 production of T cells from patients with SLE in vitro. These results indicate that defects of IL-2 synthesis of patients with SLE are at least in part due to the low DHEA activity in the serum.