In this study cannabidiol (CBD) was administered orally to determine its effects and mechanisms in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). We hypothesized that 75 mg/kg of oral CBD given for 5 days after initiation of disease would reduce EAE severity through suppression of either the early peripheral immune or late neuroimmune response. EAE was induced in C57BL/6 mice at two different magnitudes, and peripheral inflammatory and neuroinflammatory responses were measured at days 3, 10, and 18. Th1, Th17, Tc1, Tc17, Tregs, and myeloid derived suppressor cells (MDSC) were identified from the lymph nodes and spleens of each mouse to determine if CBD altered the suppressor cell or inflammatory cell populations in secondary lymphoid tissues. Additionally, neuroinflammation was identified in brain and spinal cord tissues using various immunohistochemical techniques and flow cytometry. Early treatment of EAE with oral CBD reduced clinical disease at the day 18 timepoint which correlated with a significant decrease in the percentage of MOG35-55 specific IFN-γ producing CD8+ T cells in the spleen at day 10. Analysis of both T cell infiltration and lesion size within the spinal cord also showed a moderate reduction in neuroinflammation within the central nervous system (CNS). These results provide evidence that oral CBD suppressed the peripheral immune response that precedes neuroinflammation; however, analysis of the neuroinflammatory endpoints also suggest that the modest reduction in neuroinflammation was only partially responsible for CBD's neuroprotective capability. Graphical Abstract CBD was administered orally for the first 5 days following initiation of EAE. CBD attenuated clinical disease, and we found that CBD suppressed IFN-γ producing CD8+ T cells in the spleen at day 10. There was also modest suppression of neuroinflammation. Together these data demonstrate that early, oral administration of CBD protected mice from disease, but the modest effects on neuroinflammation suggest other mechanisms participate in CBD's neuroprotective effect in EAE.

中文翻译：

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EAE 的 CBD 抑制与脾脏 IFN-γ + CD8+ T 细胞的早期抑制和神经炎症的适度抑制相关。

在这项研究中，口服大麻二酚 (CBD) 以确定其在多发性硬化症 (MS) 的实验性自身免疫性脑脊髓炎 (EAE) 模型中的作用和机制。我们假设在疾病开始后 5 天内给予 75 mg/kg 口服 CBD 将通过抑制早期外周免疫或晚期神经免疫反应来降低 EAE 严重程度。在 C57BL/6 小鼠中以两种不同的量级诱导 EAE，并在第 3、10 和 18 天测量外周炎症和神经炎症反应。鉴定了 Th1、Th17、Tc1、Tc17、Treg 和髓源性抑制细胞 (MDSC)从每只小鼠的淋巴结和脾脏中确定 CBD 是否改变了次级淋巴组织中的抑制细胞或炎症细胞群。此外，使用各种免疫组织化学技术和流式细胞术在脑和脊髓组织中鉴定出神经炎症。用口服 CBD 早期治疗 EAE 在第 18 天时间点减少了临床疾病，这与第 10 天脾脏中产生 MOG35-55 特异性 IFN-γ 的 CD8+ T 细胞的百分比显着降低相关。T 细胞浸润和分析脊髓内的病变大小也显示中枢神经系统 (CNS) 内的神经炎症适度减少。这些结果提供了证据表明口服 CBD 抑制了神经炎症之前的外周免疫反应。然而，对神经炎症终点的分析也表明，神经炎症的适度减少只是 CBD 神经保护能力的部分原因。图形摘要 CBD 在 EAE 开始后的前 5 天口服给药。CBD 减轻了临床疾病，我们发现 CBD 在第 10 天抑制了脾脏中产生 IFN-γ 的 CD8+ T 细胞。神经炎症也有适度的抑制。这些数据共同表明，早期口服 CBD 可以保护小鼠免受疾病侵害，但对神经炎症的适度影响表明其他机制参与了 CBD 在 EAE 中的神经保护作用。