Cox W I, Holbrook N J, Friedman H
J Natl Cancer Inst. 1983 Nov;71(5):973-81.
With the use of an in vitro model system, the mode of action of glucocorticoids on murine natural killer (NK) cell-mediated cytotoxicity of tumor cells was investigated. Of the steroids tested, only the glucocorticoids notably suppressed NK activity. Glucocorticoids were not toxic to the NK effector cell since inhibitors of protein synthesis protected NK activity from the suppressive action of glucocorticoids. Glucocorticoid-treated C57BL/6J spleen cells, although suppressed in NK activity, were unable to suppress the NK activity of normal syngeneic spleen cell cultures. Similarly, the supernatants of glucocorticoid-treated cultures were also unable to suppress normal NK activity. Thus a role for suppressor cell activity or soluble suppressive factors was excluded. Results of analyses of the NK activity of Percoll-fractionated glucocorticoid-treated C3H/HeN (nu/nu) spleen cells at the single-cell level demonstrated that NK effector cells could efficiently bind to YAC-1 lymphoma cells but were incapable of inducing cytolysis. Moreover, the production of NK cytotoxicity factor(s) in tumor cell-stimulated nude mouse spleen cell cultures was severely depressed after glucocorticoid treatment. The results of these studies suggest that glucocorticoids suppress murine NK activity by acting directly on the NK effector cells, possibly by inhibiting the formation or release of specific effector molecules that are cytotoxic to NK-sensitive tumor cells.
利用体外模型系统，研究了糖皮质激素对小鼠自然杀伤（NK）细胞介导的肿瘤细胞细胞毒性的作用方式。在所测试的类固醇中，只有糖皮质激素能显著抑制NK活性。糖皮质激素对NK效应细胞无毒，因为蛋白质合成抑制剂可保护NK活性免受糖皮质激素的抑制作用。经糖皮质激素处理的C57BL/6J脾细胞，尽管NK活性受到抑制，但无法抑制同基因正常脾细胞培养物的NK活性。同样，经糖皮质激素处理的培养物的上清液也无法抑制正常的NK活性。因此，排除了抑制细胞活性或可溶性抑制因子的作用。对经Percoll分级分离的糖皮质激素处理的C3H/HeN（nu/nu）脾细胞在单细胞水平上的NK活性分析结果表明，NK效应细胞能够有效地与YAC-1淋巴瘤细胞结合，但无法诱导细胞溶解。此外，糖皮质激素处理后，肿瘤细胞刺激的裸鼠脾细胞培养物中NK细胞毒性因子的产生严重受抑。这些研究结果表明，糖皮质激素可能通过直接作用于NK效应细胞来抑制小鼠的NK活性，可能是通过抑制对NK敏感肿瘤细胞具有细胞毒性的特定效应分子的形成或释放。
