Stopińska-Głuszak Urszula, Waligóra Jacek, Grzela Tomasz, Głuszak Michał, Jóźwiak Jarosław, Radomski Dariusz, Roszkowski Piotr I, Malejczyk Jacek
Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, Chałubińskiego 5, PL-02004 Warsaw, Poland.
J Reprod Immunol. 2006 Feb;69(1):65-75. doi: 10.1016/j.jri.2005.07.006. Epub 2005 Oct 19.
Sex steroids are known to affect immune responses; however, information on immunomodulatory effects of estrogen/progesterone hormone replacement therapy (HRT) is still limited. Therefore, the present study aimed to investigate the effect of estrogen/medroxyprogesterone HRT on natural killer (NK) cell cytotoxicity and immunoregulatory cytokine (IL-2, IL-4 and IFN-gamma) release by phytohemaglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) from 15 selected healthy postmenopausal women. NK cell cytotoxicity, cytokine production and serum levels of 17beta-estradiol (E2), progesterone (P) and FSH were tested in each patient before and after 90-days HRT. NK cell cytotoxicity was tested by (51)Cr-release assay using K562 erythroleukemic cells as target. Specific cytokine production and serum hormone levels were evaluated by enzyme-linked immunosorbent assay (ELISA) and immunochemiluminescent assays, respectively. HRT resulted in a significant decrease of Kupperman index, an increase of E2 and a decrease of FSH levels. These changes were associated with a significant decrease of NK cell cytotoxicity, IL-2 and IFN-gamma production. The levels of IL-4 production remained unchanged. Changes of NK cell cytotoxicity and cytokine release in individual patients did not correlate with changes of serum sex hormone levels. Nevertheless, the present results imply strongly that estrogen/progesterone HRT may affect cell-mediated immunity, thus being a potential factor influencing development and course of autoimmune disorders and neoplastic diseases.
已知性类固醇会影响免疫反应；然而，关于雌激素/孕激素激素替代疗法（HRT）免疫调节作用的信息仍然有限。因此，本研究旨在调查雌激素/甲羟孕酮HRT对15名选定的健康绝经后妇女经植物血凝素（PHA）刺激的外周血单个核细胞（PBMC）的自然杀伤（NK）细胞细胞毒性和免疫调节细胞因子（IL-2、IL-4和IFN-γ）释放的影响。在每位患者进行90天HRT前后，检测其NK细胞细胞毒性、细胞因子产生以及17β-雌二醇（E2）、孕酮（P）和促卵泡激素（FSH）的血清水平。使用K562红白血病细胞作为靶细胞，通过（51）Cr释放试验检测NK细胞细胞毒性。分别通过酶联免疫吸附测定（ELISA）和免疫化学发光测定评估特异性细胞因子产生和血清激素水平。HRT导致库珀曼指数显著降低、E2升高以及FSH水平降低。这些变化与NK细胞细胞毒性、IL-2和IFN-γ产生的显著降低相关。IL-4产生水平保持不变。个体患者中NK细胞细胞毒性和细胞因子释放的变化与血清性激素水平的变化无关。然而，目前的结果强烈表明，雌激素/孕激素HRT可能影响细胞介导的免疫，因此是影响自身免疫性疾病和肿瘤性疾病发生发展及病程的一个潜在因素。
