Gatti G, Masera R G, Pallavicini L, Sartori M L, Staurenghi A, Orlandi F, Angeli A
Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Ospedale San Luigi Gonzaga, Italy.
Brain Behav Immun. 1993 Mar;7(1):16-28. doi: 10.1006/brbi.1993.1002.
Release of pro-opiomelanocortin (POMC)-derived peptides and glucocorticoids characterizes the activation of the hypothalamic-pituitary-adrenal (HPA) axis and represents a major adaptive response to stress. Both glucocorticoids and POMC-derived hormones are known to be crucial modifiers of the immune response. Natural killer (NK) cells are a lymphocyte subset deeply involved in immunosurveillance. Cortisol, the most important glucocorticoid hormone in humans, is a well-established inhibitor, whereas the two lymphokines, immune interferon (IFN-gamma) and interleukin-2 (IL-2), are important physiological stimulators. In the present study, physiological as well as superphysiological concentrations of two POMC-derived peptides, ACTH and beta-endorphin, were shown not only to affect in vitro spontaneous and lymphokine-inducible NK activity of peripheral blood mononuclear (PBM) cells, but also to modify cortisol-mediated inhibition. NK activity was measured in a 4-h cytotoxic assay using the cell line K562 as a target, after prior incubation with ACTH (10(-8)-10(-12) M) and beta-endorphin (10(-8)-10(-14) M) in the presence or absence of cortisol (10(-6) M), IFN-gamma (325 IU/ml), and IL-2 (25 IU/ml). ACTH was ineffective in changing spontaneous NK activity at all concentrations, whereas beta-endorphin enhanced NK cytotoxicity (p < .02). The concomitant exposure of PBM cells to the two POMC-derived peptides and IFN-gamma or IL-2 significantly enhanced the lymphokine-induced boosting of NK activity. Moreover, ACTH and beta-endorphin were able to significantly reduce the cortisol-dependent inhibition (p < .05). These data are compatible with the hypothesis that POMC-derived peptides have a role in the modulation of NK cell activity. It seems likely that in cases of activation of the HPA axis, ACTH and beta-endorphin may effectively counteract the negative effects of glucocorticoids on NK cell activity, and prevent, at least in some instances, any overshooting of the glucocorticoid-dependent effect on immune cells.
促阿片-黑素细胞皮质素（POMC）衍生肽和糖皮质激素的释放是下丘脑-垂体-肾上腺（HPA）轴激活的特征，代表了对压力的主要适应性反应。已知糖皮质激素和POMC衍生激素都是免疫反应的关键调节因子。自然杀伤（NK）细胞是深度参与免疫监视的淋巴细胞亚群。皮质醇是人类最重要的糖皮质激素，是一种公认的抑制剂，而两种淋巴因子，免疫干扰素（IFN-γ）和白细胞介素-2（IL-2），是重要的生理刺激剂。在本研究中，两种POMC衍生肽促肾上腺皮质激素（ACTH）和β-内啡肽的生理浓度以及超生理浓度不仅显示出会影响外周血单核（PBM）细胞的体外自发和淋巴因子诱导的NK活性，还会改变皮质醇介导的抑制作用。在与ACTH（10^(-8)-10^(-12) M）和β-内啡肽（10^(-8)-10^(-14) M）在有或没有皮质醇（10^(-6) M）、IFN-γ（325 IU/ml）和IL-2（25 IU/ml）存在的情况下预先孵育后，使用K562细胞系作为靶标，在4小时细胞毒性试验中测量NK活性。ACTH在所有浓度下改变自发NK活性均无效，而β-内啡肽增强了NK细胞毒性（p <.02）。PBM细胞同时暴露于两种POMC衍生肽和IFN-γ或IL-2可显著增强淋巴因子诱导的NK活性增强。此外，ACTH和β-内啡肽能够显著降低皮质醇依赖性抑制（p <.05）。这些数据与POMC衍生肽在调节NK细胞活性中起作用的假设相符。在HPA轴激活的情况下，ACTH和β-内啡肽似乎可能有效抵消糖皮质激素对NK细胞活性的负面影响，并至少在某些情况下防止糖皮质激素对免疫细胞的依赖性作用过度。
