Girasole G, Jilka R L, Passeri G, Boswell S, Boder G, Williams D C, Manolagas S C
Section of Endocrinology and Metabolism, Veteran's Administration Medical Center, Indianapolis, Indiana 46202.
J Clin Invest. 1992 Mar;89(3):883-91. doi: 10.1172/JCI115668.
The effect of 17 beta-estradiol on interleukin-6 (IL-6) synthesis was examined in murine bone marrow-derived stromal cell lines, normal human bone-derived cells, and nontransformed osteoblast cell lines from mice and rats. In all these cell types IL-6 production was stimulated as much as 10,000-fold in response to the combination of recombinant interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha). Addition of 17 beta-estradiol in the cultures exerted a dose-dependent inhibition of IL-1-, TNF-, and IL-1 + TNF-induced production of bioassayable IL-6. Testosterone and progesterone (but not 17 alpha-estradiol) also inhibited IL-6, but their effective concentrations were two orders of magnitude higher than 17 beta-estradiol. 17 beta-estradiol also decreased the levels of the IL-6 mRNA. In addition, estradiol inhibited both TNF-induced IL-6 production and osteoclast development in primary bone cell cultures derived from neonatal murine calvaria. The TNF-stimulated osteoclast development was also suppressed by a neutralizing monoclonal anti-IL-6 antibody. This in vitro evidence suggests, for the first time, a mechanistic paradigm by which estrogens might exert at least part of their antiresorptive influence on the skeleton.
在小鼠骨髓来源的基质细胞系、正常人骨来源细胞以及小鼠和大鼠的未转化成骨细胞系中，研究了17β-雌二醇对白细胞介素-6（IL-6）合成的影响。在所有这些细胞类型中，重组白细胞介素-1（IL-1）和肿瘤坏死因子α（TNFα）联合作用可使IL-6产生量增加多达10000倍。在培养物中添加17β-雌二醇对IL-1、TNF和IL-1 + TNF诱导的可生物测定的IL-6产生具有剂量依赖性抑制作用。睾酮和孕酮（但不是17α-雌二醇）也抑制IL-6，但它们的有效浓度比17β-雌二醇高两个数量级。17β-雌二醇还降低了IL-6 mRNA的水平。此外，雌二醇抑制了新生小鼠颅骨来源的原代骨细胞培养物中TNF诱导的IL-6产生和破骨细胞发育。TNF刺激的破骨细胞发育也被一种中和性抗IL-6单克隆抗体所抑制。这一体外证据首次表明了一种机制模式，雌激素可能至少部分通过该模式对骨骼发挥其抗吸收作用。
