Billiau A
J Pharmacol. 1983;14 Suppl 3:105-16.
The interferon system was discovered as an antiviral defense mechanism of all higher animals. It is in many aspects complementary to the immune system in that it operates as a first line defense against virus infections by limiting viral replication wherever it occurs in the organism, hereby delaying spread of virus through the body and allowing time for the immune response to develop and become operative in due course. Studies in experimental animals and in man have indicated that administration of exogenous interferon can prevent viral disease if the interferon reaches the crucial sites of viral replication in sufficient concentration and before the virus replication starts. This fact constitutes the main impediment for interferon to become an important antiviral drug. In all animal species that have been examined, there exist multiple genes for interferon. Currently, three types (alpha, beta and gamma) of interferon are distinguished, the genes of which share minor part of their sequences. Each type can in principle comprise several subtypes which share major parts of their sequences. Interferons act on cells by altering their biochemical programming. Thereby they exert multiple cellular effects other than inhibiting virus replication. Cell growth and regeneration of organs is retarded; cells of the immune system are affected in various ways and, as a result of this, the immune system can be stimulated or suppressed depending on the experimental or clinical conditions. Some aspects of this immunoregulatory effect have led to the belief that interferon therapy might be beneficial for tumor patients. In animal systems the antitumor effect of interferon is real but limited in scope : tumors can be delayed in outgrowth but cannot be caused to regress. In clinical trials, mostly involving terminal or preterminal cancer patients, encouraging but unconvincing results have been obtained. This type of investigation is now entering into a stage where amounts of interferon can be given, comparable to those used for animal studies. Moreover, the various types and subtypes of interferon can now be produced in pure form, allowing to test them separately. It is not excluded that from these investigations, new approaches for antitumor therapy will emerge. As regulators of the immune response, interferons may play an important role in auto-immune diseases.(ABSTRACT TRUNCATED AT 400 WORDS)
干扰素系统作为所有高等动物的一种抗病毒防御机制被发现。它在许多方面与免疫系统互补,因为它作为抵御病毒感染的第一道防线,通过限制病毒在生物体中任何部位的复制来发挥作用,从而延缓病毒在体内的传播,并为免疫反应的发展和适时发挥作用留出时间。对实验动物和人类的研究表明,如果干扰素能以足够的浓度在病毒复制开始前到达病毒复制的关键部位,那么给予外源性干扰素可以预防病毒性疾病。这一事实构成了干扰素成为一种重要抗病毒药物的主要障碍。在所有已被研究的动物物种中,都存在多个干扰素基因。目前,可区分出三种类型(α、β和γ)的干扰素,它们的基因序列只有一小部分相同。原则上,每种类型都可以包含几个亚型,这些亚型的序列大部分相同。干扰素通过改变细胞的生化程序来作用于细胞。由此,它们除了抑制病毒复制外,还发挥多种细胞效应。细胞生长和器官再生受到抑制;免疫系统的细胞受到各种影响,因此,根据实验或临床情况,免疫系统可能会受到刺激或抑制。这种免疫调节作用的某些方面使人们相信,干扰素治疗可能对肿瘤患者有益。在动物实验系统中,干扰素的抗肿瘤作用是真实存在的,但范围有限:肿瘤的生长可以被延缓,但不会使其消退。在临床试验中,大多涉及晚期或接近晚期的癌症患者,虽然取得了令人鼓舞但并不令人信服的结果。这类研究目前正进入一个阶段,即可以给予与动物研究中使用的剂量相当的干扰素。此外,现在可以以纯形式生产各种类型和亚型的干扰素,从而能够分别对它们进行测试。不排除从这些研究中会出现抗肿瘤治疗的新方法。作为免疫反应的调节因子,干扰素可能在自身免疫性疾病中发挥重要作用。(摘要截选至400字)