Activation of immune function by dehydroepiandrosterone (DHEA) in age-advanced men
Activation of immune function by dehydroepiandrosterone (DHEA) in age-advanced men
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DOI：
10.1093/gerona/52a.1.m1
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发表时间：
1997-01-01
影响因子：
5.1
通讯作者：
Yen, SSC
中科院分区：
文献类型：
--
作者：
Khorram, O;Vu, L;Yen, SSC
背景动物实验的大量数据表明脱氢表雄酮（DHEA）对免疫功能具有刺激作用。然而，人们对DHEA对人体免疫系统的影响知之甚少。由于衰老与免疫功能下降和DHEA生产有关，我们提出老年男性口服DHEA将导致其免疫系统的激活。9名健康的老年男性（平均年龄63岁），低DHEA硫酸盐水平参与了这项研究。他们每晚口服安慰剂2周，然后服用DHEA（50 mg）20周。每隔4- 8周采集空腹（0800 h-0900 h）血样，用于免疫功能研究和激素测定。新鲜分离的外周血淋巴细胞用于流式细胞术鉴定淋巴细胞亚群、表达IL-2受体（IL-2 R）的细胞、促分裂原刺激研究，以及确定自然杀伤（NK）细胞数量和细胞毒性。在基础和促分裂原刺激条件下，测定培养淋巴细胞分泌的白细胞介素-2（IL-2）和IL-6水平。分析血清中可溶性IL-2受体（sIL-2 R）水平、胰岛素样生长因子-I（IGF-I）和胰岛素样生长因子结合蛋白-1（IGFBP-1）浓度。结果。血清DHEA硫酸盐（DHEAS）的基线水平（循环DHEA水平的稳定标志物）比年轻成人值低2个标准差，并在2周内增加3-4倍。这些水平在DHEA给药的整个期间持续。与安慰剂相比，DHEA给药导致血清IGF-I增加20%（p < .01），IGFBP-1呈下降趋势，IGF-I/IGFBP-1比率增加32%（p < .01）。DHEA治疗2-20周内免疫功能激活。治疗2周（45%）和20周（35%）后单核细胞数量显著增加（p <0.01）。B细胞群在治疗2周（35%）和10周（29%）时随增加而波动（p <0.05）。12周时，B细胞促有丝分裂反应增加62%（p <0.05），血清IgG、伊加和IgM水平无变化。总T细胞和T细胞亚群未改变。然而，在DHEA治疗12-20周时，发现T细胞促有丝分裂反应增加40%（p <0.05），表达IL-2 R（CD 25（+））的细胞增加39%（p <0.05），血清sIL-2 R水平增加20%（p <0.01），表明T淋巴细胞发生了功能性活化。体外促分裂原刺激的IL-2和IL-6的释放在治疗20周时分别增加了50%（p <0.05）和30%（p <0.01），而基础分泌不受影响。治疗18-20周后，NK细胞数量增加了22-37%（p < .01），同时细胞毒性增加了45%（p < .01）。DHEA administration.Conclusion，口服DHEA每日剂量50 mg，对血清DHEAS水平低的老年男性显着激活免疫功能。解释DHEA免疫增强特性的机制尚不清楚。考虑到增加生物可利用的IGF-I的潜在作用，凭借其对免疫细胞功能的促有丝分裂作用，可能介导DHEA的影响。虽然需要进一步的研究，但我们的结论表明DHEA在免疫缺陷状态下具有潜在的治疗益处。
Background. Substantial data from animal studies have demonstrated a stimulatory effect of dehydroepiandrosterone (DHEA) on immune function. However, little is known about the effects of DHEA on the human immune system. Since aging is associated with a decline in immune function and in DHEA production, we proposed that oral administration of DHEA to elderly men would result in activation of their immune system.Methods. Nine healthy age-advanced men (mean age of 63 years) with low DHEA-sulfate levels participated in this study. They were treated nightly with an oral placebo for 2 weeks followed by DHEA (50 mg) for 20 weeks. Fasting (0800h-0900h) blood samples were obtained at 4- ro 8-week intervals for immune function studies and hormone determinations. Freshly isolated peripheral lymphocytes were used for flow cytometric identification of lymphocyte subsets, cells expressing the IL-2 receptor (IL-2R), mitogen stimulation studies, and for determining natural killer (NK) cell number and cytotoxicity. Levels of interleukin-2 (IL-2) and IL-6 secreted from cultured lymphocytes were determined under basal and mitogen stimulated conditions. Sera were analyzed for soluble IL-2 Receptor (sIL-2R) levels, insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) concentrations.Results. Baseline levels of serum DHEA sulfate (DHEAS), a stable marker of circulating DHEA levels, were 2 standard deviations below young adult values and increased 3-4 fold within 2 weeks. These levels were sustained throughout the duration of DHEA administration. When compared with placebo, DHEA administration resulted in a 20% increase (p < .01) in serum IGF-I, a decreasing trend in IGFBP-1, and a 32% increase in the ratio of IGF-I IGFBP-1 (p < .01). Activation of immune function occurred within 2-20 weeks of DHEA treatment. The number of monocytes increased significantly (p < .01) after 2 (45%) and 20 (35%) weeks of treatment. The population of B cells fluctuated with increases (p < .05) at 2 (35%) and 10 (29%) weeks of treatment. B cell mitogenic response increased 62% (p < .05) by 12 weeks unaccompanied by changes in serum IgG, IgA, and IgM levels. Total T cells and T cell subsets were unaltered. However, a 40% increase (p < .05) in T cell mitogenic response, 39% increase in cells expressing the IL-2R (CD25(+)) (p < .05), and 20% increase in serum sIL-2R levels (p < .01) were found at 12-20 weeks of DHEA treatment, suggesting a functional activation of T lymphocytes occurred. In vitro mitogen stimulated release of IL-2 and IL-6 was enhanced 50% (p < .05) and 30% (p < .01) respectively by 20 weeks of treatment without basal secretion being affected. NK cell number showed a 22-37% increase (p < .01) by 18-20 weeks of treatment with a concomitant 45% increase (p < .01) in cytotoxicity. There were no adverse effects noted with DHEA administration.Conclusion, Administration of oral DHEA at a daily dose of 50 mg to age-advanced men with low serum DHEAS levels significantly activated immune function. The mechanism(s) to account for the immunoenhancing properties of DHEA are unclear. Consideration is given to the potential role of an increase in bioavailable IGF-I, which by virtue of its mitogenic effects on immune cell function, may mediate the DHEA effects. While extended studies are required, our Endings suggest potential therapeutic benefits of DHEA in immunodeficient states.