Lowy M T, Reder A T, Gormley G J, Meltzer H Y
Department of Psychiatry, Case Western Reserve University, Cleveland, OH 44106.
Biol Psychiatry. 1988 Oct;24(6):619-30. doi: 10.1016/0006-3223(88)90136-9.
The effect of in vivo (1 mg) and in vitro (10(-7)-10(-10) M) dexamethasone administration on mitogen-induced lymphocyte proliferation was examined in drug-free depressed patients, nondepressed psychiatric patients, as well as normal controls, and was related to the results of a standard overnight Dexamethasone Suppression Test (DST). The effect of oral dexamethasone administration was also examined for its effect on lymphocyte cytosolic glucocorticoid receptor content. Oral dexamethasone administration significantly decreased both phytohemagglutinin (PHA) and concanavalin A (Con-A) induced lymphocyte proliferation, as well as glucocorticoid receptor number in suppressors, whereas dexamethasone failed to decrease these responses in nonsuppressors. Nonsuppressors had significantly lower serum dexamethasone levels compared to suppressors at both 8:00 AM and 4:00 PM. However, when differences in serum dexamethasone levels were covaried out, there were still significant differences between suppressors and nonsuppressors on the dexamethasone-induced mitogen changes, but the changes in glucocorticoid receptor content were no longer significant. In vitro incubation of lymphocytes with dexamethasone produced a dose-related decrease in mitogenesis, which was not different between the depressed and nondepressed groups. However, at physiologically relevant concentrations of dexamethasone (10(-9)-10(-10) M), nonsuppressors as compared to suppressors were more resistant to the immunosuppressive effects of in vitro dexamethasone on the Con-A response. The inhibitory effect of in vitro dexamethasone on Con-A-stimulated lymphocytes was positively correlated with basal 4:00 PM cortisol values. In conclusion, in vitro techniques are useful probes to assess glucocorticoid sensitivity in depression. The present results also further support the hypothesis that glucocorticoid insensitivity is associated with DST nonsuppression.
在未服用药物的抑郁症患者、非抑郁症精神科患者以及正常对照中，研究了体内给予地塞米松（1毫克）和体外给予地塞米松（10⁻⁷ - 10⁻¹⁰摩尔/升）对丝裂原诱导的淋巴细胞增殖的影响，并将其与标准过夜地塞米松抑制试验（DST）的结果相关联。还研究了口服地塞米松对淋巴细胞胞质糖皮质激素受体含量的影响。口服地塞米松显著降低了植物血凝素（PHA）和刀豆蛋白A（Con - A）诱导的淋巴细胞增殖，以及抑制细胞中的糖皮质激素受体数量，而地塞米松未能降低非抑制细胞中的这些反应。与抑制细胞相比，非抑制细胞在上午8:00和下午4:00时的血清地塞米松水平显著较低。然而，当血清地塞米松水平的差异被校正后，在由地塞米松诱导的丝裂原变化方面，抑制细胞和非抑制细胞之间仍存在显著差异，但糖皮质激素受体含量的变化不再显著。淋巴细胞与地塞米松的体外孵育产生了与剂量相关的有丝分裂抑制作用，抑郁症组和非抑郁症组之间没有差异。然而，在地塞米松的生理相关浓度（10⁻⁹ - 10⁻¹⁰摩尔/升）下，与抑制细胞相比，非抑制细胞对体外地塞米松对Con - A反应的免疫抑制作用更具抗性。体外地塞米松对Con - A刺激的淋巴细胞的抑制作用与下午4:00的基础皮质醇值呈正相关。总之，体外技术是评估抑郁症中糖皮质激素敏感性的有用探针。目前的结果也进一步支持了糖皮质激素不敏感与DST非抑制相关的假说。
