Ralston S H, Russell R G, Gowen M
Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, England.
J Bone Miner Res. 1990 Sep;5(9):983-8. doi: 10.1002/jbmr.5650050912.
Cytokines, such as interleukin-1 (IL-1) and tumor necrosis factors (TNF), produced by cells of the monocyte-macrophage lineage in the local bone microenvironment, are potentially important local regulators of bone turnover. To investigate whether the protective effects of estrogen against postmenopausal bone loss may be mediated by inhibition of cytokine release, we studied the effects of 17 beta-estradiol, dihydrotestosterone, and hydrocortisone on TNF release from human peripheral blood mononuclear cells (PBMC) in vitro. In unstimulated cells derived from eight postmenopausal women, seven of whom had osteoporotic vertebral fractures, 17 beta-estradiol inhibited TNF release in a dose-dependent manner between 10(-6) and 10(-12) M but had no consistent effect on cells derived from men or premenopausal women. Dihydrotestosterone in concentrations of up to 10(-6) M had no effect on TNF release in any patient group, whereas hydrocortisone at 10(-6) M was a potent inhibitor of TNF release in all groups. Since TNF is a potent stimulator of bone resorption, the inhibitory effect of estrogen on TNF release may be part of the mechanism by which it exerts a protective effect on the skeleton in postmenopausal women. These observations may also be relevant in other inflammatory diseases of connective tissue, such as rheumatoid arthritis, in which disease activity may fluctuate as estrogen levels change--during the menstrual cycle, in pregnancy, and after the menopause.
细胞因子，如白细胞介素-1（IL-1）和肿瘤坏死因子（TNF），由局部骨微环境中的单核巨噬细胞系细胞产生，可能是骨转换的重要局部调节因子。为了研究雌激素对绝经后骨质流失的保护作用是否可能通过抑制细胞因子释放来介导，我们在体外研究了17β-雌二醇、二氢睾酮和氢化可的松对人外周血单核细胞（PBMC）释放TNF的影响。在来自8名绝经后妇女的未受刺激细胞中，其中7人患有骨质疏松性椎体骨折，17β-雌二醇在10^(-6)至10^(-12)M之间以剂量依赖方式抑制TNF释放，但对来自男性或绝经前妇女的细胞没有一致影响。浓度高达10^(-6)M的二氢睾酮对任何患者组的TNF释放均无影响，而10^(-6)M的氢化可的松在所有组中都是TNF释放的有效抑制剂。由于TNF是骨吸收的强效刺激剂，雌激素对TNF释放的抑制作用可能是其对绝经后妇女骨骼发挥保护作用的机制的一部分。这些观察结果在其他结缔组织炎症性疾病中可能也具有相关性，如类风湿性关节炎，在该疾病中，疾病活动可能会随着雌激素水平的变化而波动——在月经周期、怀孕期间和绝经后。
