Estrogens and autoimmune diseases
Estrogens and autoimmune diseases
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DOI：
10.1196/annals.1386.043
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Straubb, Rawer H.
中科院分区：
文献类型：
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作者：
Cutolo, Maurizio;Capellino, Silvia;Straubb, Rawer H.
性激素与免疫反应有关，雌激素至少是体液免疫的增强剂，雄激素和黄体酮（和糖皮质激素）是天然的免疫抑制剂。一些生理、病理和治疗条件可能会改变血清雌激素环境和/或外周转化率，包括月经周期、妊娠、产后期、更年期、老年、慢性压力、昼夜节律改变、炎性细胞因子以及皮质类固醇、口服避孕药和类固醇激素替代品的使用，从而引起雄激素/雌激素比例和相关效应的改变。特别是，皮质醇和褪黑激素的昼夜节律发生了改变，至少在类风湿关节炎（RA）中是如此，并且部分涉及性激素昼夜节律的合成和水平。炎症细胞因子（即 TNF-α、IL-1 和 IL-6）的产生对芳香酶活性的异常调节（即活性增加）可能部分解释了 RA 和系统性红斑狼疮中外周雌激素合成的异常（即滑液中 17-β 雌二醇和可能的代谢物的可用性增加），以及血清性激素水平和比例的改变（即雄激素和 DHEAS 减少）。在 RA 患者的滑液中，两性均观察到雌激素浓度增加，更具体地以羟基化形式为特征，特别是 16α-羟基雌酮，它是一种促有丝分裂和细胞增殖的内源激素。性激素在自身免疫性风湿性疾病中的局部作用似乎主要在于调节细胞增殖和细胞因子产生（即 TNFα、IL-1、IL-12）。在这方面，有趣的是，男性 RA 患者似乎比女性患者从抗 TNFα 策略中获益更多。
Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immune-suppressors. Several physiological, pathological, and therapeutic conditions may change the serum estrogen milieu and/or peripheral conversion rate, including the menstrual cycle, pregnancy, postpartum period, menopause, being elderly, chronic stress, altered circadian rhythms, inflammatory cytokines, and use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. In particular, cortisol and melatonin circadian rhythms are altered, at least in rheumatoid arthritis (RA), and partially involve sex hormone circadian synthesis and levels as well. Abnormal regulation of aromatase activity (i.e., increased activity) by inflammatory cytokine production (i.e., TNF-alpha, IL-1, and IL-6) may partially explain the abnormalities of peripheral estrogen synthesis in RA (i.e., increased availability of 17-beta estradiol and possible metabolites in synovial fluids) and in systemic lupus erythematosus, as well as the altered serum sex-hormone levels and ratio (i.e., decreased androgens and DHEAS). In the synovial fluids of RA patients, the increased estrogen concentration is observed in both sexes and is more specifically characterized by the hydroxylated forms, in particular 16alpha-hydroxyestrone, which is a mitogenic and cell proliferative endogenous hormone. Local effects of sex hormones in autoimmune rheumatic diseases seems to consist mainly in modulation of cell proliferation and cytokine production (i.e., TNFalpha, Il-1, IL-12). In this respect, it is interesting that male patients with RA seem to profit more from anti-TNFalpha strategies than do female patients.