Antel Jack P, Miron Veronique E
Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Clin Neurol Neurosurg. 2008 Nov;110(9):951-7. doi: 10.1016/j.clineuro.2008.03.021. Epub 2008 May 27.
To review the direct and indirect effects on the central nervous system (CNS) of systemically administered immuno-modulatory therapies in use or under evaluation for the relapsing forms of multiple sclerosis (MS).
We summarize data published by our own lab and by others that delineate the effects of such therapies on in vitro neural cell cultures and in animal model-based systems.
The long-approved therapies, interferon beta (IFNbeta) and glatiramer acetate (GA), do not readily access the CNS. These agents can still indirectly have an effect on disease-related immune regulatory and effector functions within the CNS by modulating the properties of systemic immune cells that migrate to this compartment. Such immune cells could interact with perivascular and innate immune cells that are involved in immune regulation and with cells that are either targets of the disease process (oligodendrocytes, neurons) and/or are involved with repair (progenitor cells). Newer agents reported to favorably impact on relapse frequency in MS include the sphingosine-1-phosphate agonist, fingolimod, and the lipophilic statin, simvastatin. Both agents access the CNS and thus represent examples of agents that could directly impact on disease-relevant injury and repair process within the CNS.
The observations reviewed in this report regarding indirect and direct effects of immuno-modulatory agents on the CNS indicate the need to understand and monitor the neurobiologic effects of such therapies.
回顾目前正在使用或处于评估阶段的系统性免疫调节疗法对复发型多发性硬化症（MS）中枢神经系统（CNS）的直接和间接影响。
我们总结了我们自己实验室以及其他机构发表的数据，这些数据描述了此类疗法对体外神经细胞培养和基于动物模型的系统的影响。
长期获批的疗法，即干扰素β（IFNβ）和醋酸格拉替雷（GA），不易进入中枢神经系统。这些药物仍可通过调节迁移至该区域的全身免疫细胞的特性，间接影响中枢神经系统内与疾病相关的免疫调节和效应功能。此类免疫细胞可与参与免疫调节的血管周围和固有免疫细胞以及作为疾病进程靶点的细胞（少突胶质细胞、神经元）和/或参与修复的细胞（祖细胞）相互作用。据报道，对MS复发频率有积极影响的新型药物包括鞘氨醇-1-磷酸激动剂芬戈莫德和亲脂性他汀类药物辛伐他汀。这两种药物均可进入中枢神经系统，因此代表了可直接影响中枢神经系统内与疾病相关的损伤和修复过程的药物实例。
本报告中回顾的关于免疫调节药物对中枢神经系统的间接和直接影响的观察结果表明，有必要了解和监测此类疗法的神经生物学效应。
