Edwards B S, Hawkins M J, Borden E C
J Biol Response Mod. 1983;2(5):409-17.
The relationship between interferon (IFN) stimulation of natural killer (NK) cell cytotoxicity in vitro and changes in NK cell cytotoxicity resulting from systemic IFN administration was examined in 15 cancer patients in two clinical trials. Ficoll-Hypaque-separated peripheral mononuclear cells (PMC) were incubated 18-20 h with or without IFN on 2 different days prior to therapy initiation to determine in vitro responsiveness to IFN and unstimulated basal levels of NK cell activity, respectively. Three different preparations of IFN-alpha were tested, including native Cantell IFN-alpha and two recombinant DNA-generated species, IFN-r alpha A and IFN-r alpha D. Twenty-four hours after i.m. injection of IFNs, significant NK cell activity enhancement occurred (p = 0.003). The relative extent of cytotoxicity elevation in individual patients resulting from injection significantly correlated (p less than 0.01) with the degree of NK cell activity enhancement induced in vitro by treatment of PMC with the same IFN preparation. These results suggest that patients exhibited individual differences in acute responsiveness to systemic IFN administration, which could be predicted to a certain extent by in vitro testing prior to therapy.
在两项临床试验中，对15名癌症患者进行了研究，以考察体外干扰素（IFN）刺激自然杀伤（NK）细胞细胞毒性与全身给予IFN后NK细胞细胞毒性变化之间的关系。在开始治疗前的2个不同日期，将经Ficoll-Hypaque分离的外周单个核细胞（PMC）分别在有或无IFN的情况下孵育18 - 20小时，以分别确定体外对IFN的反应性和NK细胞活性的未刺激基础水平。测试了三种不同的IFN-α制剂，包括天然的坎特尔IFN-α以及两种通过重组DNA生成的类型，即IFN-rαA和IFN-rαD。肌肉注射IFN 24小时后，NK细胞活性显著增强（p = 0.003）。注射导致的个体患者细胞毒性升高的相对程度与用相同IFN制剂处理PMC在体外诱导的NK细胞活性增强程度显著相关（p < 0.01）。这些结果表明，患者对全身给予IFN的急性反应存在个体差异，在治疗前通过体外测试可在一定程度上对此进行预测。
