Salem Mohamed Labib
Section of Surgical Oncology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.
Curr Drug Targets Inflamm Allergy. 2004 Mar;3(1):97-104. doi: 10.2174/1568010043483944.
Estrogen appears to play a central role in the immune response and immune-mediated diseases. Estrogen receptors are expressed in a variety of immunocompetent cells, including CD4(+) and CD8(+) T cells and macrophages. Clinical observations indicate that some autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, frequently remit during pregnancy but exacerbate, or have their onset during the postpartum period. Pharmacological levels of estrogen also appear to ameliorate certain autoimmune diseases. In addition, estrogen is known to suppress certain infectious diseases, as well as T cell-mediated responses toward oxazolone, keyhol lympet hemocyanin, Listeria soluble protein and purified protein derivatives. The immune basis for these phenomena is poorly understood. Based on a distinctive profile of cytokine production, data accumulated thus far have revealed modulatory effects for estrogen on the TH1-type and TH2-type cells, which represent two polarized forms of the effector specific immune response. Recent evidence indicates that estrogens inhibit the production of TH1 proinflammatory cytokines, such as IL-12, TNF-alpha and IFN-gamma, whereas they stimulate the production of TH2 anti-inflammatory cytokines, such as IL-10, IL-4, and TGF-beta. This can explain why estrogen suppresses and potentiates TH1- and TH2-mediated diseases, respectively. We hypothesize that exacerbation or suppression of inflammatory diseases by estrogen is mediated by skewing TH1-type to TH2-type response. This view represents a novel mechanism for the modulatory effect of estrogen on certain inflammatory diseases that can lead to beneficial or detrimental impacts depending on the type of immune involved. Such a concept is valuable when considering the application of combination therapies that include estrogen.
雌激素似乎在免疫反应和免疫介导的疾病中发挥核心作用。雌激素受体在多种免疫活性细胞中表达，包括CD4(+)和CD8(+) T细胞以及巨噬细胞。临床观察表明，一些自身免疫性疾病，如类风湿性关节炎和多发性硬化症，在怀孕期间常常缓解，但在产后会加重或发病。药理学水平的雌激素似乎也能改善某些自身免疫性疾病。此外，已知雌激素能抑制某些传染病，以及T细胞介导的对恶唑酮、钥孔戚血蓝蛋白、李斯特菌可溶性蛋白和纯化蛋白衍生物的反应。这些现象的免疫基础尚不清楚。基于细胞因子产生的独特特征，迄今为止积累的数据揭示了雌激素对TH1型和TH2型细胞的调节作用，这两种细胞代表效应器特异性免疫反应的两种极化形式。最近的证据表明，雌激素抑制TH1促炎细胞因子的产生，如IL-12、TNF-α和IFN-γ，而它们刺激TH2抗炎细胞因子的产生，如IL-10、IL-4和TGF-β。这可以解释为什么雌激素分别抑制和增强TH1和TH2介导的疾病。我们假设雌激素对炎症性疾病的加重或抑制是通过将TH1型反应偏向TH2型反应来介导的。这一观点代表了雌激素对某些炎症性疾病调节作用的一种新机制，根据所涉及的免疫类型，这种调节作用可能产生有益或有害的影响。在考虑应用包括雌激素的联合疗法时，这样的概念是有价值的。
