Masera R G, Staurenghi A, Sartori M L, Angeli A
Clinica Medica Generale, Dipartimento di Scienze Cliniche e Biologiche, Università degli Studi di Torino, Regione Gonzole 10, 10043 Orbassano (Torino), Italy.
Eur J Endocrinol. 1999 Apr;140(4):299-306. doi: 10.1530/eje.0.1400299.
Natural killer (NK) cells are CD3(-)CD16(+)CD56(+) bone-marrow-derived lymphocytes mediating first-line defence by direct cytotoxicity against various types of target cells without prior immunization. NK cell activity is positively regulated by immune interferon (IFN-gamma); among hormones, glucocorticoids are potent in vitro and in vivo inhibitors, whereas ACTH and beta-endorphin in many experimental circumstances enhance NK cytotoxicity.
We measured NK cytotoxicity of peripheral blood mononuclear cells (PBMC) obtained at 0800h and 2000h from 26 patients with Cushing's syndrome (12 pituitary-dependent, 12 adrenal-dependent and two dependent on ectopic ACTH secretion). In vitro responsiveness to IFN-gamma or cortisol was also tested.
NK activity was measured in a 4-h direct cytotoxicity assay using K562 cells as targets. Plasma ACTH, serum and urinary free cortisol were concomitantly measured with commercially available kits.
Spontaneous activity and responsiveness to IFN-gamma or cortisol were significantly greater in 15 age- and sex-matched controls than in Cushing's patients at 0800h. In pituitary-dependent Cushing's patients, plasma ACTH correlated positively with mean levels of spontaneous NK activity (r=0.64, P<0.05) and negatively with cortisol-dependent percentage inhibition (r=-0.69, P<0.02). In adrenal-dependent Cushing's patients, a negative correlation was observed between levels of spontaneous NK activity and urinary free cortisol (r=-0.67, P<0.02).
Our data indicate that excess endogenous glucocorticoids affect spontaneous NK cell activity and responsiveness to exogenous IFN-gamma or cortisol. The differential patterns observed between pituitary-dependent and adrenal-dependent groups are compatible with a positive immunomodulatory role of pituitary pro-opiomelanocortin-derived peptides that effectively counterbalance, at least partially, glucocorticoid immunosuppression.
自然杀伤（NK）细胞是骨髓来源的CD3(-)CD16(+)CD56(+)淋巴细胞，可在无需预先免疫的情况下通过对各种类型靶细胞的直接细胞毒性介导一线防御。NK细胞活性受免疫干扰素（IFN-γ）正向调节；在激素中，糖皮质激素在体外和体内均为强效抑制剂，而促肾上腺皮质激素（ACTH）和β-内啡肽在许多实验情况下可增强NK细胞毒性。
我们测量了26例库欣综合征患者（12例垂体依赖性、12例肾上腺依赖性和2例异位ACTH分泌依赖性）在08:00和20:00获取的外周血单个核细胞（PBMC）的NK细胞毒性。还测试了其对IFN-γ或皮质醇的体外反应性。
使用K562细胞作为靶细胞，通过4小时直接细胞毒性试验测量NK活性。使用市售试剂盒同时测量血浆ACTH、血清和尿游离皮质醇。
在08:00时，15名年龄和性别匹配的对照组的自发活性以及对IFN-γ或皮质醇的反应性显著高于库欣综合征患者。在垂体依赖性库欣综合征患者中，血浆ACTH与自发NK活性的平均水平呈正相关（r = 0.64，P < 0.05），与皮质醇依赖性抑制百分比呈负相关（r = -0.69，P < 0.02）。在肾上腺依赖性库欣综合征患者中，自发NK活性水平与尿游离皮质醇之间存在负相关（r = -0.67，P < 0.02）。
我们的数据表明，内源性糖皮质激素过量会影响自发NK细胞活性以及对外源性IFN-γ或皮质醇的反应性。垂体依赖性和肾上腺依赖性组之间观察到的差异模式与垂体阿片黑素皮质素原衍生肽的正向免疫调节作用相符，该作用可有效至少部分抵消糖皮质激素的免疫抑制作用。
