Bowes Amy L, Yip Ping K
Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London , London, United Kingdom .
J Neurotrauma. 2014 Nov 1;31(21):1753-66. doi: 10.1089/neu.2014.3429. Epub 2014 Sep 8.
Spinal cord injury can have a range of debilitating effects, permanently impacting a patient's quality of life. Initially thought to be an immune privileged site, the spinal cord is able to mount a timely and well organized inflammatory response to injury. Intricate immune cell interactions are triggered, typically consisting of a staggered multiphasic immune cell response, which can become deregulated if left unchecked. Although several immunomodulatory compounds have yielded success in experimental rodent spinal cord injury models, their translation to human clinical studies needs further consideration. Because temporal differences between rodent and human inflammatory responses to spinal cord injury do exist, drug delivery timing will be a crucial component in recovery from spinal cord injury. Given too early, immunomodulatory therapies may impede beneficial inflammatory reactions to the injured spinal cord or even miss the opportunity to dampen delayed harmful autoimmune processes. Therefore, this review aims to summarize the temporal inflammatory response to spinal cord injury, as well as detailing specific immune cell functions. By clearly defining the chronological order of inflammatory events after trauma, immunomodulatory drug delivery timing can be better optimized. Further, we compare spinal cord injury-induced inflammatory responses in rodent and human studies, enabling clinicians to consider these differences when initiating clinical trials. Improved understanding of the cellular immune response after spinal cord injury would enhance the efficacy of immunomodulatory agents, enabling combined therapies to be considered.
脊髓损伤会产生一系列使人衰弱的影响，永久性地影响患者的生活质量。脊髓最初被认为是一个免疫豁免部位，但它能够对损伤及时发起组织良好的炎症反应。复杂的免疫细胞相互作用被触发，通常包括一个交错的多相免疫细胞反应，如果不加以控制，这种反应可能会失调。尽管几种免疫调节化合物在实验性啮齿动物脊髓损伤模型中取得了成功，但将它们应用于人类临床研究还需要进一步考虑。由于啮齿动物和人类对脊髓损伤的炎症反应确实存在时间差异，药物递送时间将是脊髓损伤恢复的关键因素。给药过早，免疫调节疗法可能会阻碍对受损脊髓的有益炎症反应，甚至错过抑制延迟性有害自身免疫过程的机会。因此，本综述旨在总结对脊髓损伤的时间性炎症反应，并详细阐述特定免疫细胞的功能。通过明确界定创伤后炎症事件的时间顺序，可以更好地优化免疫调节药物的递送时间。此外，我们比较了啮齿动物和人类研究中脊髓损伤诱导的炎症反应，使临床医生在启动临床试验时能够考虑这些差异。对脊髓损伤后细胞免疫反应的更好理解将提高免疫调节药物的疗效，从而能够考虑联合治疗。
