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视神经脊髓炎谱系疾病中嗜酸性粒细胞的趋化因子和细胞因子升高。

Elevated chemokines and cytokines for eosinophils in neuromyelitis optica spectrum disorders.

机构信息

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China.

出版信息

Mult Scler Relat Disord. 2021 Jul;52:102940. doi: 10.1016/j.msard.2021.102940. Epub 2021 Apr 9.

Abstract

BACKGROUND

Eosinophil infiltration is one of the distinctive features in neuromyelitis optica spectrum disorders (NMOSD) but not in other demyelinating diseases including multiple sclerosis (MS). Eosinophils express the chemokine receptor CCR3, which is activated by eotaxins (eotaxin-1, -2, and -3) and monocyte chemoattractant protein (MCP)-4. We aimed to investigate the role of MCPs (MCP-1, -2, -3, and -4) and eotaxins in the acute phase of NMOSD.

METHODS

Levels of serum and cerebrospinal fluid (CSF) eotaxins, MCPs, interleukin (IL)-5, tumor necrosis factor (TNF)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-6 were measured using the cytokine multiplex assay from 26 patients with NMOSD (13 with immunotherapy, 13 without immunotherapy), 9 patients with MS, and 9 patients with other noninflammatory neurological diseases (OND). Glial fibrillary acidic protein was assessed using ELISA.

RESULTS

Serum MCP-1 and CSF MCP-2 levels were significantly higher in patients with NMOSD than in OND. Moreover, serum MCP-4 and CSF eotaxin-2 and -3 levels were significantly higher in NMOSD patients compared to MS and OND. Serum MCP-1, -4 and CSF eotaxin-2, -3 levels were significantly correlated with the Expanded Disability Status Scale in NMOSD. TNF-α and GM-CSF, which stimulate the above chemokines, were higher in patients with NMOSD than those in OND. Moreover, serum MCP-1 and -4 were significantly increased by IL-5 and GM-CSF stimulation, but not by TNF-α and IL-6. Only CSF eotaxin-2 was significantly increased by GM-CSF. There were no significant differences in serum MCP-1 and -4 levels between NMOSD patients with and without immunotherapy.

CONCLUSION

These findings suggest that the elevated serum MCP-1, -4 and CSF eotaxin-2, -3 may be a key step in eosinophil recruitment in the acute phase of NMOSD.

摘要

背景

嗜酸性粒细胞浸润是视神经脊髓炎谱系疾病(NMOSD)的特征之一,但不是多发性硬化症(MS)等脱髓鞘疾病的特征。嗜酸性粒细胞表达趋化因子受体 CCR3,该受体被嗜酸性粒细胞趋化因子(嗜酸性粒细胞趋化因子-1、-2 和-3)和单核细胞趋化蛋白(MCP)-4 激活。我们旨在研究 MCP(MCP-1、-2、-3 和-4)和嗜酸性粒细胞趋化因子在 NMOSD 急性期的作用。

方法

采用细胞因子多重分析检测 26 例 NMOSD 患者(13 例接受免疫治疗,13 例未接受免疫治疗)、9 例 MS 患者和 9 例其他非炎症性神经疾病(OND)患者的血清和脑脊液(CSF)嗜酸性粒细胞趋化因子、MCP、白细胞介素(IL)-5、肿瘤坏死因子(TNF)-α、粒细胞-巨噬细胞集落刺激因子(GM-CSF)和 IL-6 的水平。使用 ELISA 法检测神经胶质纤维酸性蛋白。

结果

与 OND 患者相比,NMOSD 患者的血清 MCP-1 和 CSF MCP-2 水平明显升高。此外,与 MS 和 OND 患者相比,NMOSD 患者的血清 MCP-4 和 CSF 嗜酸性粒细胞趋化因子-2 和-3 水平明显升高。NMOSD 患者的血清 MCP-1、-4 和 CSF 嗜酸性粒细胞趋化因子-2、-3 水平与扩展残疾状况量表显著相关。NMOSD 患者的 TNF-α和 GM-CSF 高于 OND 患者,这两种细胞因子可刺激上述趋化因子。此外,IL-5 和 GM-CSF 可显著增加血清 MCP-1 和-4,但 TNF-α和 IL-6 则不能。只有 GM-CSF 可显著增加 CSF 嗜酸性粒细胞趋化因子-2。NMOSD 患者接受和未接受免疫治疗的患者之间血清 MCP-1 和-4 水平无显著差异。

结论

这些发现表明,血清 MCP-1、-4 和 CSF 嗜酸性粒细胞趋化因子-2、-3 的升高可能是 NMOSD 急性期嗜酸性粒细胞募集的关键步骤。

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