Dhib-Jalbut Suhayl
Department of Neurology, University of Maryland School of Medicine, Baltimore VA Medical Center, Baltimore, MD, USA.
Neurology. 2002 Apr 23;58(8 Suppl 4):S3-9. doi: 10.1212/wnl.58.8_suppl_4.s3.
MS is an immunologically mediated disease, as determined by observation of the response to immunotherapy and the existence of an animal model, experimental autoimmune encephalitis. Interferon (IFN) beta-1b, IFN beta-1a, and glatiramer acetate, the therapies used for relapsing or remitting MS, have mechanisms of action that address the immunologic pathophysiology of MS. The IFNs bind to cell surface-specific receptors, initiating a cascade of signaling pathways that end with the secretion of antiviral, antiproliferative, and immunomodulatory gene products. Glatiramer acetate, a synthetic molecule, inhibits the activation of myelin basic protein-reactive T cells and induces a T-cell repertoire characterized by anti-inflammatory effects. Although the two classes of drugs have some overlapping mechanisms of action, the IFNs rapidly block blood-brain barrier leakage and gadolinium (Gd) enhancement within 2 weeks, whereas glatiramer acetate produces less rapid resolution of Gd-enhanced MRI activity. IFN beta has no direct effects in the CNS, but glatiramer acetate-specific T cells are believed to have access to the CNS, where they can exert anti-inflammatory and possibly neuroprotective effects.
多发性硬化症（MS）是一种免疫介导的疾病，这是通过观察免疫治疗的反应以及动物模型实验性自身免疫性脑脊髓炎的存在而确定的。干扰素（IFN）β-1b、IFNβ-1a和醋酸格拉替雷，这些用于复发型或缓解型MS的疗法，其作用机制针对MS的免疫病理生理学。干扰素与细胞表面特异性受体结合，引发一系列信号通路，最终分泌抗病毒、抗增殖和免疫调节基因产物。醋酸格拉替雷是一种合成分子，可抑制髓鞘碱性蛋白反应性T细胞的激活，并诱导具有抗炎作用的T细胞库。尽管这两类药物有一些重叠的作用机制，但干扰素可在2周内迅速阻止血脑屏障渗漏和钆（Gd）增强，而醋酸格拉替雷对Gd增强的MRI活性的消退作用较慢。IFNβ在中枢神经系统中没有直接作用，但醋酸格拉替雷特异性T细胞被认为可以进入中枢神经系统，在那里它们可以发挥抗炎作用并可能具有神经保护作用。
