Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Iran.
Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Iran.
Arch Med Res. 2014 Feb;45(2):177-82. doi: 10.1016/j.arcmed.2014.01.002. Epub 2014 Jan 28.
A large body of studies has shown that 17-β estradiol (E2) has a protective effect on susceptibility to experimental autoimmune encephalomyelitis (EAE). Clinical improvement in multiple sclerosis and its animal model, EAE, during pregnancy, when estrogen levels are high, suggests an immunomodulatory role for estrogens. The immune basis for this protection is poorly understood. In this study we evaluated the effect of E2 on the synthesis of inflammatory, antiinflammatory and regulatory cytokines.
We analyzed the effect of E2 on IL-4, IL-10, IL-17, TNF-α and IFN-γ cytokines produced by proteolipid protein (PLP) or mitogen phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells isolated from multiple sclerosis patients in comparison to healthy control group. We used RT-PCR and ELISA to detect the level of cytokines.
We found that E2 significantly increased IL-10 expression and secretion and decreased expression of TNF-α in both groups and IL-4 in patients in cells stimulated with PLP or PHA (p <0.0001).
These data indicated that E2 could affect expression and secretion of inflammatory and anti-inflammatory cytokines and could regulate immune responses especially in the differentiation towards regulatory responses, and this finding might have therapeutic value in multiple sclerosis.
大量研究表明，17-β雌二醇（E2）对实验性自身免疫性脑脊髓炎（EAE）的易感性具有保护作用。在多发性硬化症及其动物模型 EAE 期间，妊娠时雌激素水平升高，临床症状得到改善，这表明雌激素具有免疫调节作用。这种保护的免疫基础知之甚少。在这项研究中，我们评估了 E2 对炎症、抗炎和调节性细胞因子合成的影响。
我们分析了 E2 对多发性硬化症患者和健康对照组外周血单个核细胞中由髓鞘蛋白（PLP）或丝裂原植物血凝素（PHA）激活产生的 IL-4、IL-10、IL-17、TNF-α 和 IFN-γ 细胞因子的影响。我们使用 RT-PCR 和 ELISA 检测细胞因子的水平。
我们发现 E2 可显著增加 PLP 或 PHA 刺激的细胞中两组的 IL-10 表达和分泌，并降低 TNF-α 的表达，以及患者组中 IL-4 的表达（p<0.0001）。
这些数据表明，E2 可以影响炎症和抗炎细胞因子的表达和分泌，并调节免疫反应，特别是在向调节性反应的分化方面，这一发现可能对多发性硬化症具有治疗价值。
