Lotzová E, Savary C A, Quesada J R, Gutterman J U, Hersh E M
J Natl Cancer Inst. 1983 Nov;71(5):903-10.
Peripheral blood natural killer (NK) cell cytotoxicity of 24 cancer patients was studied prior to and after single and multiple injections of various doses of human leukocyte recombinant interferon-alpha clone A (IFN-alpha rA). The NK cell cytotoxicity of all cancer patients declined consistently 4 and 8 hours after a single injection of IFN-alpha rA. Twenty-four hours after the injection of IFN-alpha rA, NK cell cytotoxicity of patients with low NK cell phenotype (NK-LR) was significantly augmented, whereas that of patients with medium (NK-MR) or high (NK-HR) NK phenotype was depressed. After multiple injections of IFN-alpha rA, depression of NK cell cytotoxicity was observed in a number of NK-MR and NK-HR patients, but in some patients with NK-LR phenotype, further potentiation was observed. No direct correlation between the NK cell augmentation and serum IFN levels was detected. In in vitro studies, IFN-alpha rA, when added to cultures of target and effector cells of normal individuals in a dose of 10(3) U/ml, was efficient in augmenting NK cell cytotoxicity. NK cell cytotoxicity of cancer patients could also be augmented by the IFN-alpha rA preparation; however, this augmentation occurred only prior to in vivo IFN-alpha rA therapy. After IFN-alpha rA in vivo therapy, their NK cells became refractory to further in vitro IFN-alpha rA treatment.
研究了24例癌症患者在单次和多次注射不同剂量的人白细胞重组干扰素-α克隆A(IFN-α rA)之前和之后外周血自然杀伤(NK)细胞的细胞毒性。所有癌症患者在单次注射IFN-α rA后4小时和8小时,NK细胞毒性持续下降。注射IFN-α rA后24小时,低NK细胞表型(NK-LR)患者的NK细胞毒性显著增强,而中(NK-MR)或高(NK-HR)NK表型患者的NK细胞毒性则降低。多次注射IFN-α rA后,许多NK-MR和NK-HR患者出现NK细胞毒性降低,但在一些NK-LR表型患者中,观察到进一步增强。未检测到NK细胞增强与血清IFN水平之间的直接相关性。在体外研究中,当以10(3) U/ml的剂量将IFN-α rA添加到正常个体的靶细胞和效应细胞培养物中时,可有效增强NK细胞毒性。癌症患者的NK细胞毒性也可通过IFN-α rA制剂增强;然而,这种增强仅发生在体内IFN-α rA治疗之前。在体内进行IFN-α rA治疗后,其NK细胞对进一步的体外IFN-α rA治疗变得不敏感。