Mire-Sluis A R, Page L A, Meager A, Igaki J, Lee J, Lyons S, Thorpe R
Division of Immunobiology, National Institute for Biological Standards and Control, Potters Bar, Hertfordshire, U.K.
J Immunol Methods. 1996 Sep 9;195(1-2):55-61. doi: 10.1016/0022-1759(96)00092-0.
Interferons-alpha and -beta (IFN-alpha and -beta) are cytokines that are widely known to induce potent anti-viral activity. However, it has become increasingly apparent that IFN-alpha and -beta exert a variety of other biological effects, including anti-tumour and immunomodulatory activities and are increasingly used clinically to treat a range of malignancies, myelodysplasias and autoimmune diseases, e.g., IFN-beta for multiple sclerosis. The most widely used bioassays for the IFNs are based on their anti-viral activity, but these do not predict the biological activity of the IFNs in anti-tumour and immunomodulatory therapies. Thus, we have developed anti-cytokine-based bioassays that may be more reflective of such activity and which have several advantages over existing anti-viral bioassays. The anti-cytokine bioassay is based on the ability of IFN-alpha, -beta and -omega to inhibit granulocyte-macrophage-colony-stimulating factor (GM-CSF) induced proliferation of the erythroleukaemic cell line TF-1. This assay can take only 24 h, is sensitive to 200 fg (0.04 IU) IFN-alpha or -beta and 100 fg (0.02 IU) IFN-omega and is able to detect down to these levels in serum or plasma samples. The usefulness of anti-cytokine bioassays for IFN-alpha, -beta and -omega is not restricted to the GM-CSF/TF-1 cell format and other alternatives are available, such as erythropoietin (EPO)/TF-1 cells and EPO/UT-7-EPO cells. These assays can be made specific for each of the IFNs by including neutralising antibodies in the bioassay.
α-干扰素和β-干扰素（IFN-α和IFN-β）是细胞因子，众所周知它们可诱导强大的抗病毒活性。然而，越来越明显的是，IFN-α和IFN-β发挥多种其他生物学效应，包括抗肿瘤和免疫调节活性，并且在临床上越来越多地用于治疗一系列恶性肿瘤、骨髓增生异常综合征和自身免疫性疾病，例如用于治疗多发性硬化症的IFN-β。针对干扰素最广泛使用的生物测定法基于它们的抗病毒活性，但这些方法无法预测IFN在抗肿瘤和免疫调节治疗中的生物学活性。因此，我们开发了基于抗细胞因子的生物测定法，这种方法可能更能反映此类活性，并且与现有的抗病毒生物测定法相比具有多个优势。抗细胞因子生物测定法基于IFN-α、IFN-β和IFN-ω抑制粒细胞-巨噬细胞集落刺激因子（GM-CSF）诱导的红白血病细胞系TF-1增殖的能力。该测定法仅需24小时，对200 fg（0.04 IU）的IFN-α或IFN-β以及100 fg（0.02 IU）的IFN-ω敏感，并且能够在血清或血浆样品中检测到这些水平。针对IFN-α、IFN-β和IFN-ω的抗细胞因子生物测定法的用途并不局限于GM-CSF/TF-1细胞形式，还有其他替代方法可用，例如促红细胞生成素（EPO）/TF-1细胞和EPO/UT-7-EPO细胞。通过在生物测定中加入中和抗体，这些测定法可以针对每种干扰素进行特异性检测。
