Panitch H S
Neurology Service, VA Medical Center, Baltimore, Maryland.
Drugs. 1992 Dec;44(6):946-62. doi: 10.2165/00003495-199244060-00004.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, characterised clinically by relapses and remissions, and leading eventually to chronic disability. Despite an enormous amount of research, the cause of MS remains unknown; however, pathological, genetic, and immunological features have been identified that suggest the disease has an autoimmune basis. Accordingly, current therapy of MS includes corticotrophin or corticosteroids for acute exacerbations, and more potent immunosuppressive drugs for severe cases unresponsive to steroids. All of these agents can cause serious adverse reactions. There is an urgent need for immunotherapy that is less toxic, that can be given early and perhaps indefinitely, and that will prevent relapses and progression of the disease. Our current knowledge of the effects of interferons (IFNs) in MS is based on the results of laboratory research and clinical therapeutic trials carried out over the past decade. Existing evidence points to the conclusion that the effects of the IFNs in MS are mediated by immunoregulatory rather than antiviral or nonspecific mechanisms. Administration of IFN gamma increases the exacerbation rate, and IFN gamma as well as other cytokines may be involved in the pathogenesis of MS lesions. In contrast, studies of IFN beta show that it tends to inhibit the activity of IFN gamma and appears to prevent disease activity. Intrathecal administration of IFN beta, although effective, is cumbersome and potentially hazardous. A large multicentre placebo-controlled trial of systemic recombinant IFN beta was recently conducted in the US, and the results of the first 2 years of treatment were considered sufficiently encouraging that an application for licensing was submitted to the Food and Drug Administration in June 1992. If approved, it will be the first new agent licensed for clinical use in MS in over 20 years. The study will continue under double-blind conditions for at least another year, and a second trial of systemic recombinant IFN beta therapy is also in progress. These studies should provide definitive answers to questions about the role of IFNs in the pathogenesis of MS, as well as the place of recombinant IFN beta as an effective therapeutic agent.
多发性硬化症（MS）是一种中枢神经系统的炎性脱髓鞘疾病，临床特征为复发和缓解，并最终导致慢性残疾。尽管进行了大量研究，但MS的病因仍不明确；不过，已确定的病理、遗传和免疫学特征表明该疾病具有自身免疫基础。因此，目前MS的治疗方法包括用于急性加重期的促肾上腺皮质激素或皮质类固醇，以及用于对类固醇无反应的严重病例的更强效免疫抑制药物。所有这些药物都可能引起严重的不良反应。迫切需要毒性较小、可早期给药且可能长期给药、能预防疾病复发和进展的免疫疗法。我们目前对干扰素（IFN）在MS中作用的了解基于过去十年进行的实验室研究和临床治疗试验结果。现有证据表明，IFN在MS中的作用是通过免疫调节而非抗病毒或非特异性机制介导的。给予γ干扰素会增加病情加重率，γ干扰素以及其他细胞因子可能参与MS病变的发病机制。相比之下，对β干扰素的研究表明，它倾向于抑制γ干扰素的活性，似乎能预防疾病活动。鞘内注射β干扰素虽然有效，但操作繁琐且有潜在危险。美国最近进行了一项大型多中心系统性重组β干扰素安慰剂对照试验，前两年的治疗结果被认为足够令人鼓舞，因此于1992年6月向食品药品管理局提交了上市许可申请。如果获批，它将成为20多年来首个被批准用于MS临床治疗的新药。该研究将在双盲条件下至少再持续一年，另一项系统性重组β干扰素治疗试验也在进行中。这些研究应能为IFN在MS发病机制中的作用以及重组β干扰素作为有效治疗药物的地位等问题提供明确答案。
