Straub Rainer H
Laboratory of Experimental Rheumatology and Neuroendocrino-Immunology, Division of Rheumatology, Department of Internal Medicine I, University Hospital, 93042 Regensburg, Germany.
Endocr Rev. 2007 Aug;28(5):521-74. doi: 10.1210/er.2007-0001. Epub 2007 Jul 19.
There is still an unresolved paradox with respect to the immunomodulating role of estrogens. On one side, we recognize inhibition of bone resorption and suppression of inflammation in several animal models of chronic inflammatory diseases. On the other hand, we realize the immunosupportive role of estrogens in trauma/sepsis and the proinflammatory effects in some chronic autoimmune diseases in humans. This review examines possible causes for this paradox. This review delineates how the effects of estrogens are dependent on criteria such as: 1) the immune stimulus (foreign antigens or autoantigens) and subsequent antigen-specific immune responses (e.g., T cell inhibited by estrogens vs. activation of B cell); 2) the cell types involved during different phases of the disease; 3) the target organ with its specific microenvironment; 4) timing of 17beta-estradiol administration in relation to the disease course (and the reproductive status of a woman); 5) the concentration of estrogens; 6) the variability in expression of estrogen receptor alpha and beta depending on the microenvironment and the cell type; and 7) intracellular metabolism of estrogens leading to important biologically active metabolites with quite different anti- and proinflammatory function. Also mentioned are systemic supersystems such as the hypothalamic-pituitary-adrenal axis, the sensory nervous system, and the sympathetic nervous system and how they are influenced by estrogens. This review reinforces the concept that estrogens have antiinflammatory but also proinflammatory roles depending on above-mentioned criteria. It also explains that a uniform concept as to the action of estrogens cannot be found for all inflammatory diseases due to the enormous variable responses of immune and repair systems.
关于雌激素的免疫调节作用，仍然存在一个尚未解决的矛盾。一方面，在几种慢性炎症性疾病的动物模型中，我们认识到雌激素对骨吸收的抑制作用以及对炎症的抑制作用。另一方面，我们也了解到雌激素在创伤/脓毒症中的免疫支持作用以及在人类某些慢性自身免疫性疾病中的促炎作用。本综述探讨了这一矛盾的可能原因。本综述阐述了雌激素的作用如何取决于以下标准：1）免疫刺激（外来抗原或自身抗原）以及随后的抗原特异性免疫反应（例如，雌激素抑制T细胞与激活B细胞）；2）疾病不同阶段所涉及的细胞类型；3）具有特定微环境的靶器官；4）17β-雌二醇给药时间与疾病进程（以及女性的生殖状态）的关系；5）雌激素的浓度；6）雌激素受体α和β的表达变异，这取决于微环境和细胞类型；7）雌激素的细胞内代谢导致产生具有截然不同的抗炎和促炎功能的重要生物活性代谢产物。还提到了一些全身超系统，如下丘脑-垂体-肾上腺轴、感觉神经系统和交感神经系统，以及它们如何受到雌激素的影响。本综述强化了这样一种观念，即根据上述标准，雌激素具有抗炎作用，但也具有促炎作用。它还解释了由于免疫和修复系统的巨大可变反应，无法为所有炎症性疾病找到关于雌激素作用的统一概念。
