Brown S L, Van Epps D E
J Immunol. 1985 May;134(5):3384-90.
The opioid peptides beta-endorphin and met-enkephalin have been shown to modulate human lymphocyte proliferation, mononuclear cell locomotion, natural killer cell activity, and neutrophil locomotion. This study demonstrates that beta-endorphin and met-enkephalin inhibit the production of a T lymphocyte chemotactic factor (LCF) by concanavalin A (Con A)-stimulated peripheral blood mononuclear cells. Inhibition of LCF production was observed by using concentrations of 10(-11) to 10(-6) M beta-endorphin or met-enkephalin but not alpha-endorphin. A bimodal pattern of suppression of LCF production was observed with both met-enkephalin and beta-endorphin when titrated from 10(-12) to 10(-6) M concentrations, with the peaks of suppressive activity occurring at concentrations of 10(-11) M and 10(-6) M. Timed studies of the production of LCF over a 54-hr period showed that there was an appreciable lag in the onset of measurable LCF activity in mononuclear supernatants produced in the presence of beta-endorphin and met-enkephalin. The suppression of LCF production mediated by opioid peptides in mononuclear supernatants was abrogated by depletion of glass-adherent mononuclear cells before culturing with opioids and Con A. The inhibitory effect of opioid peptides on LCF production was prevented by the addition of indomethacin to cell cultures. Additional experiments showed that exogenous prostaglandin E2 (PGE2) suppressed Con A-stimulated LCF production when added at concentrations ranging from 10(-6) to 10(-8) M. Other studies suggested that the mechanism of opioid peptide-mediated suppression of LCF production was due to an enhanced sensitivity of mononuclear cells to the inhibitory action of PGE2. These data provide further evidence for modulation of the immune response in humans by the neuroendocrine hormones beta-endorphin and met-enkephalin and further suggest a link between this modulation and arachidonic acid metabolism.
阿片肽β-内啡肽和甲硫氨酸脑啡肽已被证明可调节人类淋巴细胞增殖、单核细胞运动、自然杀伤细胞活性和中性粒细胞运动。本研究表明，β-内啡肽和甲硫氨酸脑啡肽可抑制伴刀豆球蛋白A（Con A）刺激的外周血单核细胞产生T淋巴细胞趋化因子（LCF）。使用10^(-11)至10^(-6) M浓度的β-内啡肽或甲硫氨酸脑啡肽可观察到LCF产生受到抑制，但α-内啡肽则无此作用。当甲硫氨酸脑啡肽和β-内啡肽从10^(-12)至10^(-6) M浓度进行滴定处理时，观察到LCF产生的抑制呈现双峰模式，抑制活性峰值出现在10^(-11) M和10^(-6) M浓度处。对54小时内LCF产生的定时研究表明，在存在β-内啡肽和甲硫氨酸脑啡肽的情况下产生的单核细胞上清液中，可测量的LCF活性开始出现明显延迟。在用阿片肽和Con A培养之前，通过去除玻璃黏附单核细胞，可消除阿片肽介导的单核细胞上清液中LCF产生的抑制作用。向细胞培养物中添加吲哚美辛可防止阿片肽对LCF产生的抑制作用。额外的实验表明，当以10^(-6)至10^(-8) M的浓度添加外源性前列腺素E2（PGE2）时，可抑制Con A刺激的LCF产生。其他研究表明，阿片肽介导的LCF产生抑制机制是由于单核细胞对PGE2抑制作用的敏感性增强。这些数据为神经内分泌激素β-内啡肽和甲硫氨酸脑啡肽对人类免疫反应的调节提供了进一步证据，并进一步表明这种调节与花生四烯酸代谢之间存在联系。
