Khan O A, Jiang H, Subramaniam P S, Johnson H M, Dhib-Jalbut S S
Department of Neurology, University of Maryland School of Medicine, Baltimore, USA.
Mult Scler. 1998 Apr;4(2):63-9. doi: 10.1177/135245859800400204.
The interferons (IFN) are a family of complex proteins possessing antiviral, antiproliferative, and immunomodulatory activities. Two type I recombinant human IFN have been recently approved for the treatment of multiple sclerosis (MS). However, use of high dose type I IFN treatment in MS patients has been limited by dose-related toxicity. Ovine IFN tau is a unique type I interferon discovered for its role in the animal reproductive cycle. It differs from other type I IFNs in that it is remarkably less toxic even at high concentrations, is able to cross species barriers, and is not inducible by viral infection. Ovine IFN tau has been shown to be very effective in the treatment of animal models of MS. In this study, we examined the toxicity of OvIFN tau on human T-cells at high doses and its immunregulatory properties at equivalent doses. Our experiments confirmed the remarkably non-toxic nature of OvIFN tau on human cells at high concentrations as well as immunomodulating properties consistent with other type I IFNs including an antilymphoproliferative effect and inhibition of IFN gamma-induced HLA class II expression. These results suggest that OvIFN tau could be developed into a potentially less toxic therapeutic option for immune-mediated disorders including MS.
干扰素（IFN）是一类具有抗病毒、抗增殖和免疫调节活性的复杂蛋白质家族。两种I型重组人干扰素最近已被批准用于治疗多发性硬化症（MS）。然而，在MS患者中使用高剂量I型干扰素治疗受到剂量相关毒性的限制。绵羊干扰素τ是一种独特的I型干扰素，因其在动物生殖周期中的作用而被发现。它与其他I型干扰素的不同之处在于，即使在高浓度下其毒性也显著较低，能够跨越物种屏障，并且不会被病毒感染诱导。绵羊干扰素τ已被证明在治疗MS动物模型方面非常有效。在本研究中，我们检测了高剂量绵羊干扰素τ对人T细胞的毒性及其在等效剂量下的免疫调节特性。我们的实验证实了高浓度下绵羊干扰素τ对人细胞具有显著的无毒性质，以及与其他I型干扰素一致的免疫调节特性，包括抗淋巴细胞增殖作用和抑制干扰素γ诱导的HLA II类分子表达。这些结果表明，绵羊干扰素τ可被开发成为一种潜在毒性较低的治疗选择，用于包括MS在内的免疫介导疾病。
