Foster G R, Rodrigues O, Ghouze F, Schulte-Frohlinde E, Testa D, Liao M J, Stark G R, Leadbeater L, Thomas H C
Department of Medicine, Imperial College of Science, Technology and Medicine, St Mary's Hospital, London, UK.
J Interferon Cytokine Res. 1996 Dec;16(12):1027-33. doi: 10.1089/jir.1996.16.1027.
Interferon-alpha (IFN-alpha) subtypes were separated by HPLC from the IFN mixtures produced by virus-stimulated human lymphoblastoid cells and leukocytes. Together with preparations of lymphoblastoid IFN and recombinant IFN-beta, these were tested in three human tumor cell lines derived from liver, lung, and neuroblasts. Their relative antiviral activities differed markedly: subtype IFN-alpha 8 was the most potent and IFN-alpha 1 the least. The results were broadly similar in all three cells, with some minor differences. when the same preparations were tested for inhibition of thymidine incorporation, the relative activities were quite different: subtypes IFN-alpha 10, IFN-alpha 17, IFN-alpha 21, and IFN-alpha 5 were now the most active, and IFN-alpha 2 was the least active. IFN-alpha 1 and IFN-alpha 8 had comparable intermediate activity. Thus, the differences in activity were not caused by degradation of some subtypes during their separation. IFN-alpha 8 not only had the greatest antiviral activity but also, like IFN-beta, induced an antiviral state in U1 mutant cell lines, which lack the tyrosine kinase, Tyk2, required for signal transduction by other IFN-alpha subtypes.
通过高效液相色谱法（HPLC）从病毒刺激的人淋巴母细胞和白细胞产生的干扰素混合物中分离出α干扰素（IFN-α）亚型。将这些亚型与淋巴母细胞干扰素制剂和重组β干扰素一起，在源自肝脏、肺和神经母细胞的三种人类肿瘤细胞系中进行测试。它们的相对抗病毒活性差异显著：IFN-α8亚型活性最强，IFN-α1亚型活性最弱。在所有三种细胞中的结果大致相似，但存在一些细微差异。当测试相同制剂对胸苷掺入的抑制作用时，相对活性则大不相同：IFN-α10、IFN-α17、IFN-α21和IFN-α5亚型现在活性最高，而IFN-α2亚型活性最低。IFN-α1和IFN-α8具有相当的中等活性。因此，活性差异并非由某些亚型在分离过程中的降解所致。IFN-α8不仅具有最强的抗病毒活性，而且与IFN-β一样，能在缺乏其他IFN-α亚型信号转导所需的酪氨酸激酶Tyk2的U1突变细胞系中诱导抗病毒状态。
