Universitiy Medicine, Institute of Immunology and Transfusion Medicine, Greifswald, Germany.
Acta Neurol Scand. 2014 Jan;129(1):1-12. doi: 10.1111/ane.12165. Epub 2013 Jul 15.
The treatment of ischemic stroke is one of the great challenges in modern neurology. The localization and the size of the infarct determine the long-term disability of stroke survivors. Recent observations have revealed that stroke also alters the function of the immune system and vice versa: At the site of the infarct, a local inflammatory response develops that enhances brain lesion development. In experimental stroke, proof-of-concept studies confirm that inhibition of this immune response reduces lesion volume and improves outcome. In the peripheral blood of stroke patients, though, lymphocytopenia and monocyte dysfunction develop. These changes reflect a clinically relevant impairment of bacterial defense mechanisms because they are associated with an enhanced risk to acquire post-stroke infections. Stress hormones have been identified as important mediators of stroke-induced immune suppression. The pharmacological inhibition of beta adrenergic receptors, but not the inhibition of steroids, is effective in reducing infection and improving clinical outcome in experimental stroke; catecholamine release therefore appears causally related to stroke-induced immune suppression. Strong evidence supports the hypothesis that these immune alterations impact the clinical course of stroke patients. Thus, the development of new therapeutic strategies targeted to alter the immunological consequences of stroke appears promising. However, to date, the beneficial effects seen in experimental stroke have not been successfully translated into a clinical trial. This brief review summarizes the current understanding of the immunological consequences of ischemic stroke. Finally, we propose a concept that links the peripheral immune suppression with the development of local inflammation.
缺血性脑卒中的治疗是现代神经病学的重大挑战之一。梗死的定位和大小决定了脑卒中幸存者的长期残疾程度。最近的观察结果表明，脑卒中还会改变免疫系统的功能，反之亦然：在梗死部位，会发生局部炎症反应，从而加剧脑损伤的发展。在实验性脑卒中研究中，概念验证研究证实，抑制这种免疫反应可减少病灶体积并改善预后。然而，脑卒中患者的外周血中会出现淋巴细胞减少和单核细胞功能障碍。这些变化反映了细菌防御机制的临床相关损伤，因为它们与获得脑卒中后感染的风险增加有关。应激激素已被确定为脑卒中引起的免疫抑制的重要介质。β肾上腺素受体的药理学抑制，而不是类固醇的抑制，在实验性脑卒中后可有效降低感染风险并改善临床预后；因此，儿茶酚胺的释放似乎与脑卒中引起的免疫抑制有因果关系。大量证据支持这样一种假设，即这些免疫改变会影响脑卒中患者的临床病程。因此，开发针对改变脑卒中免疫后果的新治疗策略似乎很有希望。然而，迄今为止，在实验性脑卒中研究中观察到的有益效果尚未成功转化为临床试验。这篇简要综述总结了目前对缺血性脑卒中免疫后果的认识。最后，我们提出了一个概念，将外周免疫抑制与局部炎症的发展联系起来。
