Verheul H A, Verveld M, Hoefakker S, Schuurs A H
Organon Scientific Development Group, Oss, The Netherlands.
Immunopharmacol Immunotoxicol. 1995 Feb;17(1):163-80. doi: 10.3109/08923979509052727.
Sex hormones affect (auto)immune responses in various ways. Investigations of the effects of estrogens have produced contradictory results. We studied the effects of gender, gonadectomy and of (supra)physiological doses of (the orally active) ethinylestradiol (EE) in two spontaneous autoimmune disease models: the NZB/NZW F1 and NOD mice. In both models we confirmed the female preponderance and the aggravating effects of gonadectomy in males but not in females. The accelerated mortality found in NZB/W mice treated with supraphysiological doses of EE was not associated with increased proteinuria, increased IgG-type anti-DNA levels or increased mononuclear cell infiltrations in the submandibular gland. In contrast, we found a severe reduction in body weight and in the weights of various organs (indications of toxicity), and a decrease rather than an increase in proteinuria and in mononuclear cell infiltrations (indications for autoimmunity). Physiological doses of EE did not significantly affect disease symptoms. In the NOD model a near-physiological, non-toxic dose of EE did not cause consistent changes on immunological disease symptoms either. Therefore, we conclude that the sexual dichotomy in spontaneous autoimmune models is due to protective effects of androgens and that the mortality by estrogens is due to toxic effects rather than accelerated autoimmunity.
性激素以多种方式影响（自身）免疫反应。关于雌激素作用的研究产生了相互矛盾的结果。我们在两种自发性自身免疫疾病模型（NZB/NZW F1和NOD小鼠）中研究了性别、性腺切除术以及（超）生理剂量的（口服活性）炔雌醇（EE）的作用。在这两种模型中，我们证实了雌性占优势以及性腺切除术对雄性而非雌性的加重作用。用超生理剂量的EE处理的NZB/W小鼠中发现的加速死亡与蛋白尿增加、IgG型抗DNA水平升高或下颌下腺单核细胞浸润增加无关。相反，我们发现体重和各种器官重量严重减轻（毒性迹象），蛋白尿和单核细胞浸润减少而非增加（自身免疫迹象）。生理剂量的EE对疾病症状没有显著影响。在NOD模型中，接近生理、无毒剂量的EE也未对免疫疾病症状产生一致的变化。因此，我们得出结论，自发性自身免疫模型中的性别二分法是由于雄激素的保护作用，而雌激素导致的死亡是由于毒性作用而非自身免疫加速。
