Gallo Daniela, Battaglia Alessandra, Mantuano Elisabetta, Travaglia Daniele, De Stefano Ilaria, Buzzonetti Alexia, Scambia Giovanni
Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
Menopause. 2008 Jul-Aug;15(4 Pt 1):718-25. doi: 10.1097/gme.0b013e318167b92a.
This study was designed to compare the effects of 17beta-estradiol (17beta-E2) and a phytoestrogen-containing soy extract on the immune system in an ovariectomized rat model of menopause. Specifically, T- and B-lymphocyte subsets, the balance of type 1 and 2 immune responses in the mesenteric lymph nodes, and serum levels of different classes of immunoglobulin were examined as study endpoints.
Ovariectomized rats were treated with either the phytoestrogen-containing soy extract (50 or 100 mg/kg/day PO), 17beta-E2 (0.5 mg/kg/day PO), or vehicle; a sham control was included in the study. After the rats were killed, mesenteric lymph nodes and blood samples were collected. B- and T (CD4 and CD8)-lymphocyte subsets in mesenteric lymph nodes were evaluated by flow cytometry analysis. Cytokine-producing T lymphocytes were identified within each T-lymphocyte subset as TH1 (interferon-gamma CD4), TH2 (interleukin-4 CD4), TC1 (interferon-gamma CD8), and TC2 (interferon-4 CD8) lymphocytes. Serum levels of immunoglobulin classes were determined by enzyme-linked immunosorbent assay.
There were no differences in the proportions of B lymphocytes and CD4 and CD8 T lymphocytes among groups. Treatment with 17beta-E2 and phytoestrogen-containing soy extract induced a reduction in TH1 and TC1 lymphocytes paralleled by a slight, nonsignificant, increase in the frequency of TH2. Data expressed as TH1/TH2 and TC1/TC2 ratios depicted a significant polarization of local immunity toward a humoral response. Evaluation of immunoglobulin serum levels did not show any significant difference among groups.
Here we show that estrogens and soy phytochemicals similarly polarize the immune system toward a type 2 immune response in a preclinical model of menopause; our data draw attention to the crucial need to evaluate in clinical studies the potential side effects on the immune system of the complex soy products that are actually consumed in the postmenopausal setting.
本研究旨在比较17β-雌二醇（17β-E2）和含植物雌激素的大豆提取物对去卵巢大鼠更年期模型免疫系统的影响。具体而言，研究终点为检测T和B淋巴细胞亚群、肠系膜淋巴结中1型和2型免疫反应的平衡以及不同类别的免疫球蛋白血清水平。
将去卵巢大鼠分别用含植物雌激素的大豆提取物（50或100毫克/千克/天，口服）、17β-E2（0.5毫克/千克/天，口服）或赋形剂进行处理；研究中纳入假手术对照组。大鼠处死后，收集肠系膜淋巴结和血液样本。通过流式细胞术分析评估肠系膜淋巴结中的B和T（CD4和CD8）淋巴细胞亚群。在每个T淋巴细胞亚群中，将产生细胞因子的T淋巴细胞鉴定为TH1（干扰素-γ CD4）、TH2（白细胞介素-4 CD4）、TC1（干扰素-γ CD8）和TC2（干扰素-4 CD8）淋巴细胞。通过酶联免疫吸附测定法测定免疫球蛋白类别的血清水平。
各组间B淋巴细胞以及CD4和CD8 T淋巴细胞的比例无差异。用17β-E2和含植物雌激素的大豆提取物处理导致TH1和TC1淋巴细胞减少，同时TH2频率略有增加但无统计学意义。以TH1/TH2和TC1/TC2比值表示的数据显示局部免疫明显向体液反应极化。免疫球蛋白血清水平评估在各组间未显示任何显著差异。
我们在此表明，在更年期临床前模型中，雌激素和大豆植物化学物质同样使免疫系统向2型免疫反应极化；我们的数据提请注意在临床研究中评估绝经后实际食用的复合大豆产品对免疫系统潜在副作用的迫切需要。
