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

脱氢表雄酮缺乏对人类系统性红斑狼疮 T 细胞白细胞介素 2 生成受损的作用

基本信息

批准号：
04670398
负责人：
SUZUKI Noboru
金额：
$ 1.34万
依托单位：
St.Marianna University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670398/
关键词：
Dehydroepiandrosterone Systemic lupus erythematosus Interleukin 2 Therapy mRNA T lymphocytes CD4+ T cells IL-2 IL-2mRNA

项目摘要

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.

IL-2缺乏是鼠狼疮和人系统性红斑狼疮（SLE）的共同特征，其主要原因仍不清楚。我们自己以及其他人最近的研究表明，脱氢表雄酮（DHEA），睾酮合成的中间化合物，显着上调T细胞的IL-2的生产和外源DHEA或IL-2通过牛痘构建体给药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DHEA水平，以测试异常DHEA活性是否与患者的IL-2缺乏有关。我们发现，几乎所有接受检查的患者的血清DHEA水平都很低。DHEA水平的降低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，因为在疾病发作时抽取的血清样本中，没有皮质类固醇治疗也含有低水平的DHEA。此外，外源性DHEA在体外恢复了SLE患者T细胞受损的IL-2产生。这些结果表明，SLE患者IL-2合成的缺陷至少部分是由于血清中DHEA活性低所致。