Panitch H S
Department of Veterans Affairs Medical Center, Baltimore, Maryland, USA.
Mult Scler. 1995;1 Suppl 1:S17-21.
Recent reports of the successful treatment of relapsing-remitting MS with interferon beta-1b (IFN-beta) have ushered in a new era of immunotherapy. In a sense, this was the result of a remarkable conjunction of molecular biotechnology, immunology and clinical research, resulting in the first therapeutic agent to alter the course of this previously untreatable disease. In more concrete terms, the use of IFN-beta in MS was the logical outcome of a series of clinical trials of natural and recombinant IFNs carried out over the past decade, and of concurrent laboratory research suggesting that the effects of the IFNs in MS are mediated by immunoregulatory rather than antiviral or antiproliferative mechanisms. It is now known that the proinflammatory cytokines IFN-gamma and tumor necrosis factor alpha (TNF-alpha) are probably involved in the pathogenesis of MS lesions. In contrast, type I IFNs (alpha and beta) tend to inhibit the activity of IFN-gamma and to prevent disease activity. The earliest controlled studies of natural IFN-alpha and IFN-beta, carried out in the early 1980s, led to the phase III clinical trial of systemic recombinant IFN-beta (Betaseron), recently completed in the United States and Canada. In patients treated with high-dose IFN-beta there were significant reductions in relapse rate and in the appearance of new lesions on magnetic resonance imaging (MRI). The US Food and Drug Administration approved Betaseron for treatment of relapsing-remitting MS in 1993, and it is now in widespread clinical use. A trial of another recombinant IFN-beta, given by intramuscular injection once a week, was also recently completed. The results of this study are awaited with great interest because the primary end point was progression of disability rather than relapse rate. Meanwhile, recombinant IFN-alpha was reported to prevent relapses and MRI changes in a small but well-designed trial. In this paper, the early clinical studies and some of the immunological developments leading to the use of IFN-beta in MS are reviewed.
近期关于用干扰素β-1b（IFN-β）成功治疗复发缓解型多发性硬化症（MS）的报道开创了免疫治疗的新时代。从某种意义上说，这是分子生物技术、免疫学与临床研究显著结合的成果，催生出了首个能改变这种既往无法治疗疾病进程的治疗药物。更具体地讲，IFN-β在MS治疗中的应用是过去十年间一系列天然和重组IFN临床试验以及同期实验室研究的合理结果，这些研究表明IFN在MS中的作用是由免疫调节机制介导的，而非抗病毒或抗增殖机制。现已明确，促炎细胞因子IFN-γ和肿瘤坏死因子α（TNF-α）可能参与了MS病灶的发病机制。相比之下，I型IFN（α和β）往往会抑制IFN-γ的活性并预防疾病活动。20世纪80年代初开展的最早的天然IFN-α和IFN-β对照研究，促成了系统性重组IFN-β（倍泰龙）的III期临床试验，该试验最近在美国和加拿大完成。在接受高剂量IFN-β治疗的患者中，复发率以及磁共振成像（MRI）上新病灶的出现均显著减少。1993年，美国食品药品监督管理局批准倍泰龙用于治疗复发缓解型MS，目前该药已广泛应用于临床。另一项每周一次肌肉注射的重组IFN-β试验最近也已完成。由于主要终点是残疾进展而非复发率，人们对这项研究的结果极为期待。与此同时，在一项规模虽小但设计精良的试验中，有报道称重组IFN-α可预防复发和MRI改变。本文将对导致IFN-β用于MS治疗的早期临床研究及一些免疫学进展进行综述。
