INVITRO EFFECTS OF DIETHYLSTILBESTROL AND THE LHRH ANALOG LEUPROLIDE ON NATURAL-KILLER CELL-ACTIVITY
INVITRO EFFECTS OF DIETHYLSTILBESTROL AND THE LHRH ANALOG LEUPROLIDE ON NATURAL-KILLER CELL-ACTIVITY
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DOI：
10.1016/0162-3109(88)90056-2
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发表时间：
1988-03-01
期刊：
影响因子：
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通讯作者：
GONDER, MJ
中科院分区：
文献类型：
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作者：
ABLIN, RJ;BARTKUS, JM;GONDER, MJ
在雌激素免疫生物学后遗症的一系列研究中，评价了己烯雌酚（DES）和促黄体激素释放激素亮丙瑞林（Lupron）对自然杀伤（NK）细胞裂解活性的体外作用。将Ficoll-Hypaque梯度分离的人外周血单核细胞（PBMC）与不同浓度的DES和亮丙瑞林预孵育，并在51 Cr释放试验中评价人红白血病K-562细胞系的裂解程度。与未处理的PBMC相比，用DES预孵育的PBMC显示NK细胞裂解K-562靶细胞的能力降低82%，而亮丙瑞林的增加可忽略不计（p < 0.001）。DES或亮丙瑞林的抑制作用不是由于细胞毒性，因为孵育18和24 h（分别对应于DES/亮丙瑞林预孵育时间和NK细胞试验）的PBMC活力与未处理（对照）细胞相当。这些观察结果表明DES对免疫监视组分的进一步抑制作用。在评价亮丙瑞林对NK细胞对其他靶细胞的活性以及其他免疫反应性参数的影响之前，亮丙瑞林可能被证明是DES的有利替代品，因为其临床副作用减少，并且对免疫系统无有害作用。在亮丙瑞林有效治疗的情况下，维持肿瘤-宿主平衡和一定程度的免疫能力可能有利于前列腺癌患者获得更有效的治疗。亮丙瑞林的有效治疗可能禁忌DES诱导的免疫抑制，可能允许某些前列腺癌患者进一步选择辅助免疫治疗。
In a series of studies of the immunobiological sequelae of oestrogens, the in-vitro effect of diethylstilboestrol (DES) and the luteinizing-hormone-releasing-hormone leuprolide (Lupron) on the lytic activity of natural killer (NK) cells have been evaluated. Ficoll-Hypaque gradient-isolated human peripheral blood mononuclear cells (PBMC) were pre-incubated with varying concentrations of DES and leuprolide and the degree of lysis for the human erythroleukemia K-562 cell line was evaluated in a 51Cr-release assay. PBMC pre-incubated with DES exhibited an 82% reduction in the ability of NK cells to lyse K-562 target cells compared with a negligible 3% increase with leuprolide (p < 0.001) vs. untreated PBMC. The inhibitory effects of DES or leuprolide were not due to cytotoxicity since the viability of PBMC incubated for 18 and 24 h (corresponding to the DES/leuprolide preincubation time and the NK cell assay, respectively) was comparable to that of untreated (control) cells. These observations demonstrate the further suppressive effects of DES on components of immunosurveillance. Pending evaluation of the effect of leuprolide on the activity of NK cells for other target cells, and other parameters of immunologic responsiveness, leuprolide may prove to be a favourable alternative to DES, both in view of its reduced clinical side-effects, and because of the suggested absence of deleterious effects to the immune system. Maintenance of tumour-host equilibrium, and some degree of immunocompetency, in the presence of effective therapy with leuprolide, may prove beneficial in achieving more effective therapy in prostate cancer patients. Possibly contra-indicated by DES-induced immunosuppression, effective therapy with leuprolide may permit the further option of adjuvant immunotherapy in some patients with prostate cancer.