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重组干扰素治疗癌症患者的自然杀伤细胞细胞毒性分析

Analysis of natural killer cell cytotoxicity of cancer patients treated with recombinant interferon.

作者信息

Lotzová E, Savary C A, Quesada J R, Gutterman J U, Hersh E M

出版信息

J Natl Cancer Inst. 1983 Nov;71(5):903-10.

PMID:6580490
Abstract

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.

摘要

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。

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