Friedman D, Netti F, Schreiber A D
J Clin Invest. 1985 Jan;75(1):162-7. doi: 10.1172/JCI111669.
Although the disproportionate frequency of several immunologic disorders among women is well recognized, the effect of sex steroids on immunologic processes is unclear. We used an animal model, which has helped to elucidate the effect of corticosteroids in vivo, to quantitatively assess the effect of estradiol and steroid analogues on the immune clearance of IgG-coated erythrocytes. While corticosteroids impaired the clearance of IgG-coated erythrocytes, estradiol, in doses comparable to those achieved during pregnancy, significantly enhanced the clearance. Estradiol, however, did not enhance the splenic clearance of heat-altered erythrocytes. Splenic macrophages isolated from estradiol-treated animals expressed enhanced receptor affinity for the Fc portion of immunoglobulin G [Fc(IgG)], an effect probably responsible for the enhanced in vivo clearance. No consistent effect of estradiol on the splenic macrophage C3 receptors was observed. The synthetic androgen danazol, the mineralocorticoid deoxycorticosterone, and the cortisol metabolite tetrahydrocortisone did not alter the clearance of IgG-coated cells after 7 d of therapy. The estrogen antagonist/agonist tamoxifen enhanced the clearance of IgG-coated cells, but to a lesser extent than estradiol. An effect of estrogens on macrophage Fc (IgG) receptor-mediated clearance may explain in part the variation in clinical expression of several autoimmune disorders during changes in hormonal state, such as pregnancy.
尽管女性中几种免疫紊乱的发生率过高已得到充分认识，但性类固醇对免疫过程的影响尚不清楚。我们使用了一种动物模型，该模型有助于阐明皮质类固醇在体内的作用，以定量评估雌二醇和类固醇类似物对IgG包被红细胞免疫清除的影响。虽然皮质类固醇会损害IgG包被红细胞的清除，但与怀孕期间达到的剂量相当的雌二醇能显著增强清除作用。然而，雌二醇并未增强热改变红细胞的脾脏清除。从接受雌二醇治疗的动物中分离出的脾脏巨噬细胞对免疫球蛋白G（IgG）的Fc部分表现出增强的受体亲和力，这一效应可能是体内清除增强的原因。未观察到雌二醇对脾脏巨噬细胞C3受体有一致的影响。合成雄激素达那唑、盐皮质激素脱氧皮质酮和皮质醇代谢物四氢皮质醇在治疗7天后并未改变IgG包被细胞的清除。雌激素拮抗剂/激动剂他莫昔芬增强了IgG包被细胞的清除，但程度低于雌二醇。雌激素对巨噬细胞Fc（IgG）受体介导的清除的影响可能部分解释了几种自身免疫性疾病在激素状态变化（如怀孕）期间临床表达的差异。
