Department of Neurology, Second Affiliated Hospital; Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong 271000, China.
Department of Neurology, Caoxian People's Hospital, Heze, Shandong 061000, China.
ACS Chem Neurosci. 2021 Feb 3;12(3):430-440. doi: 10.1021/acschemneuro.0c00611. Epub 2021 Jan 21.
Subarachnoid hemorrhage (SAH) is considered a devastating disease, leaving survivors with lifelong neurological impairment. With increased knowledge that regulatory T cells (Tregs) provide protection against stroke, novel agents which could expand Treg populations have been assessed in terms of the potential clinical neuroprotection effect. Using a rat SAH model, we investigated the number variation of Tregs induced by SAH and the protective effect of low-dose interleukin-2 (IL-2) treatment on the SAH model. We observed that the number of peripheral Tregs significantly decreased soon after SAH, accompanying with reactivity recovery after 3 days. Our results also revealed that low-dose IL-2 treatment not only elevated Tregs numbers but significantly reduced neuronal injury and improved neurological functions up to 21 days (d) after SAH. Furthermore, compared with PBS-treatment group, cerebral proinflammatory factors and peripheral neutrophils were significantly suppressed by low-dose IL-2 after SAH. Therefore, the results suggest that low-dose IL-2 treatment is a novel and clinically feasible immunotherapy to improve long-term outcomes after SAH, perhaps via up-regulating Treg population to suppress neuroinflammation induced by SAH.
蛛网膜下腔出血(SAH)被认为是一种破坏性疾病,使幸存者终生存在神经功能障碍。随着越来越多的人认识到调节性 T 细胞(Tregs)对中风有保护作用,人们已经评估了新型药物,这些药物可以通过扩大 Treg 群体来评估其潜在的临床神经保护作用。本研究采用大鼠 SAH 模型,研究了 SAH 诱导的 Treg 数量变化以及低剂量白细胞介素-2(IL-2)治疗对 SAH 模型的保护作用。结果显示,SAH 后外周 Treg 数量明显减少,3 天后反应性恢复。结果还表明,低剂量 IL-2 治疗不仅可增加 Treg 数量,而且可显著减轻神经元损伤,并在 SAH 后 21 天(d)显著改善神经功能。此外,与 PBS 治疗组相比,SAH 后低剂量 IL-2 可显著抑制脑内促炎因子和外周中性粒细胞。因此,结果表明,低剂量 IL-2 治疗是一种改善 SAH 后长期预后的新型、可行的免疫疗法,可能通过上调 Treg 群体来抑制 SAH 引起的神经炎症。