The therapeutic potential of interleukin-10 in neuroimmune diseases.
The therapeutic potential of interleukin-10 in neuroimmune diseases.
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DOI：
10.1016/j.neuropharm.2014.10.020
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发表时间：
2015-09
影响因子：
4.7
通讯作者：
Watkins LR
中科院分区：
文献类型：
--
作者：
Kwilasz AJ;Grace PM;Serbedzija P;Maier SF;Watkins LR
神经免疫性疾病具有不同的症状和病因，但都涉及影响正常中枢神经系统信号传导的病理性炎症。重要的是，许多神经免疫疾病还涉及白介素-10（IL-10）的信号传导/生物利用度不足。IL-10是由免疫细胞和神经胶质细胞释放的有效抗炎细胞因子，其驱动多种抗炎过程的调节。本文将重点介绍IL-10的信号通路和功能，目前的证据表明，IL-10信号传导/生物利用度在神经免疫疾病中的不利影响，以及基于IL-10的治疗方法来治疗这些问题的影响。我们将详细回顾四种病理作为这种疾病状态的常见病因的例子，即神经性疼痛（神经创伤），骨关节炎（外周炎症），帕金森病（神经变性）和多发性硬化症（自身免疫性）。已经开发了许多增加IL-10的方法（例如，蛋白质施用、病毒载体、裸质粒DNA、包装在聚合物中以增强其进入靶细胞的摄取的质粒DNA，以及腺苷2A激动剂），这也将被讨论。一般来说，基于IL-10的疗法在治疗与各种神经免疫疾病相关的症状和病理方面都是有效的，更复杂的基于基因治疗的方法在单次注射后产生持续数月的持续治疗效果。这些令人兴奋的结果导致IL-10靶向治疗剂被定位于即将到来的治疗神经免疫性疾病（包括神经性疼痛）的临床试验。尽管需要进一步研究以确定与基于IL-10的治疗相关的全部效应，但有证据表明IL-10可能是治疗神经免疫疾病的无价靶点。本文是题为“神经免疫学和突触功能”的特刊的一部分。
Neuroimmune diseases have diverse symptoms and etiologies but all involve pathological inflammation that affects normal central nervous system signaling. Critically, many neuroimmune diseases also involve insufficient signaling/bioavailability of interleukin-10 (IL-10). IL-10 is a potent anti-inflammatory cytokine released by immune cells and glia, which drives the regulation of a variety of anti-inflammatory processes. This review will focus on the signaling pathways and function of IL-10, the current evidence for insufficiencies in IL-10 signaling/bioavailability in neuroimmune diseases, as well as the implications for IL-10-based therapies to treating such problems. We will review in detail four pathologies as examples of the common etiologies of such disease states, namely neuropathic pain (nerve trauma), osteoarthritis (peripheral inflammation), Parkinson’s disease (neurodegeneration), and multiple sclerosis (autoimmune). A number of methods to increase IL-10 have been developed (e.g. protein administration, viral vectors, naked plasmid DNA, plasmid DNA packaged in polymers to enhance their uptake into target cells, and adenosine 2A agonists), which will also be discussed. In general, IL-10-based therapies have been effective at treating both the symptoms and pathology associated with various neuroimmune diseases, with more sophisticated gene therapy-based methods producing sustained therapeutic effects lasting for several months following a single injection. These exciting results have resulted in IL-10-targeted therapeutics being positioned for upcoming clinical trials for treating neuroimmune diseases, including neuropathic pain. Although further research is necessary to determine the full range of effects associated with IL-10-based therapy, evidence suggests IL-10 may be an invaluable target for the treatment of neuroimmune disease. This article is part of a Special Issue entitled ‘Neuroimmunology and Synaptic Function’.
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