Holsapple M P, Munson A E, Munson J A, Bick P H
J Pharmacol Exp Ther. 1983 Oct;227(1):130-8.
The effect of the nonsteroidal estrogenic compound, diethylstilbestrol (DES) on cell-mediated immunocompetence in the mouse has been assessed. Adult female B6C3F1 mice were injected (s.c.) with 0.2, 1.0 and 4.0 mg/kg of DES daily for 14 days. All immunological tests and toxicological parameters were determined at least 24 hr after the last exposure. Thymic involution and hepatomegaly were noted at the lowest dose of DES. The most sensitive indicator of immunosuppression by DES was the delayed hypersensitivity response (DHR) to keyhole limpet hemocyanin in mice sensitized without adjuvant. The lowest dose of DES produced a 93% decrease, compared with a 39% decrease for the same DHR model in mice sensitized to keyhole limpet hemocyanin plus adjuvant and a 63% decrease for the DHR to sheep erythrocytes. A 35% decrease of the acute inflammatory response to carrageenin was produced by the lowest dose of DES. Day 2 proliferative responses to both concanavalin A and phytohemagglutinin (T-cell mitogens) were depressed by the lowest dose of DES, whereas significant suppression of the response to lipopolysaccharide (B-cell mitogen) was only noted at the highest dose of DES. The effects of DES on Day 3 proliferative responses were less dramatic. The mixed lymphocyte response was significantly suppressed by 1.0 and 4.0 mg/kg of DES on all days in culture. The reversibility of the DES effects was studied by resting the mice for 30 days between exposure and measuring a given parameter. All effects on organ weights and the depression of both the sheep erythrocytes DHR and the carrageenin inflammatory response were reversed.
已评估了非甾体雌激素化合物己烯雌酚（DES）对小鼠细胞介导免疫能力的影响。成年雌性B6C3F1小鼠每天皮下注射0.2、1.0和4.0毫克/千克的DES，持续14天。所有免疫测试和毒理学参数均在最后一次接触后至少24小时测定。在DES最低剂量时观察到胸腺萎缩和肝肿大。DES免疫抑制的最敏感指标是对无佐剂致敏小鼠的钥孔戚血蓝蛋白的迟发型超敏反应（DHR）。DES最低剂量使该反应降低了93%，相比之下，对钥孔戚血蓝蛋白加佐剂致敏小鼠的相同DHR模型降低了39%，对绵羊红细胞的DHR降低了63%。DES最低剂量使对角叉菜胶的急性炎症反应降低了35%。DES最低剂量使第2天对刀豆球蛋白A和植物血凝素（T细胞有丝分裂原）的增殖反应受到抑制，而仅在DES最高剂量时才观察到对脂多糖（B细胞有丝分裂原）反应的显著抑制。DES对第3天增殖反应的影响较小。在培养的所有天数中，1.0和4.0毫克/千克的DES均显著抑制混合淋巴细胞反应。通过在接触之间让小鼠休息30天并测量给定参数来研究DES作用的可逆性。对器官重量的所有影响以及对绵羊红细胞DHR和角叉菜胶炎症反应的抑制均得到逆转。
