Kamio E, Sakamoto Y, Kimura T, Takakuwa H, Sakurai M, Hosokawa J I, Nakagawa K, Yoshida F, Tagami K
Laboratory of Sport and Exercise Health, University of Tsukuba, Ibaraki, Japan.
Immunology. 1997 Nov;92(3):407-11. doi: 10.1046/j.1365-2567.1997.00363.x.
There is a controversy on the effects of physiological levels of glucocorticoids on natural killer (NK) cytotoxity. Therefore, the effects of exogenously administered dexamethasone on NK cytotoxity in 8-week-old male, Fischer 344 rats were studied. We suppose that the reason for the controversy is insufficient sensitivity of the ordinal radioactive chromium-release assay for normal healthy subjects or animals. Therefore, we developed a new index, a resistance to artificial immunosuppressor, cyclosporine A (CsA) using rat NK activity as an indicator, and named this index, increased resistance to immunosuppressor (IRIS). After some basic, characterizing studies, authors confirmed the fact that continuous doses of dexamethasone (DEX) attenuated NK suppression of CsA. In protocol 4, 18 rats were randomly divided into three groups: the first (DEX + CsA) was injected for 5 days with 0.1 mg DEX/kg/day and a single dose of CsA on the final day, intraperitoneally; the second (SAL + CsA) was treated with an equal volume of saline and CsA; the third (DEX + SAL) was treated with DEX but not CsA. The IRIS in NK activity was increased significantly (P < 0.01) with 5 days injection of DEX. These results demonstrated that physiological, and continuous dosage of glucocorticoids stimulated IRIS in NK activity in rats, and this suggests that appropriate stimuli through the hypothalamic-adrenal axis might be acting, at least, as a defence against immune collapses or dysfunctions.
糖皮质激素生理水平对自然杀伤（NK）细胞毒性的影响存在争议。因此，我们研究了外源性给予地塞米松对8周龄雄性Fischer 344大鼠NK细胞毒性的影响。我们推测，争议的原因在于常规放射性铬释放试验对正常健康受试者或动物的敏感性不足。因此，我们开发了一种新指标，以大鼠NK活性为指标，对人工免疫抑制剂环孢素A（CsA）的抗性，并将该指标命名为免疫抑制剂抗性增强（IRIS）。经过一些基础的特征研究后，作者证实了连续给予地塞米松（DEX）可减弱CsA对NK的抑制作用这一事实。在方案4中，18只大鼠被随机分为三组：第一组（DEX + CsA）连续5天腹腔注射0.1 mg DEX/kg/天，并在最后一天注射单剂量CsA；第二组（SAL + CsA）用等量生理盐水和CsA处理；第三组（DEX + SAL）用DEX处理但不使用CsA。连续5天注射DEX后，NK活性中的IRIS显著增加（P < 0.01）。这些结果表明，生理剂量且持续给药的糖皮质激素可刺激大鼠NK活性中的IRIS，这表明通过下丘脑 - 肾上腺轴的适当刺激可能至少起到了抵御免疫崩溃或功能障碍的作用。
