Effects of intravenous pulse methylprednisolone in neuromyelitis optica during the acute phase

IF 4.4 2区医学 Q1 CLINICAL NEUROLOGY

Annals of Clinical and Translational Neurology Pub Date : 2024-09-02 DOI:10.1002/acn3.52188

Shengnan Wang, Mengru Xue, Jianglong Wang, Rui Wu, Yanqing Shao, Ke Luo, Jiacheng Liu, Mingqin Zhu

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引用次数: 0

Abstract

Background

Neuromyelitis optica spectrum disorder (NMOSD) is an anti-aquaporin 4 (anti-AQP4) autoantibodies-mediated idiopathic inflammatory demyelinating disease of the central nervous system. While intravenous pulse methylprednisolone (IVMP) is the recommended initial treatment option for acute onset NMOSD, its therapeutic mechanism remains unclear. We hypothesized that IVMP would reduce the expression of pro-inflammatory factors and increase the resolution of inflammation in patients with NMOSD.

Methods

Mendelian randomization (MR) analysis was used to screen meaningful inflammatory and resolution factors for inclusion. Three MR methods with inverse variance weighting (IVW) were primarily used to identify positive results. Interleukin (IL)-10, IL-1β, IL-6, C-X-C motif chemokine ligand 12 (CXCL12), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were screened from 41 inflammatory factors, and resolvin D1 (RvD1), maresin 1 (MaR1), and lipoxin A4 (LXA4) were screened from 6 resolution markers for inclusion. Subsequently, 12 patients with NMOSD were enrolled and treated with IVMP. Serum levels of the aforementioned inflammatory and resolution markers were measured by enzyme-linked immunosorbent assay before and after IVMP treatment.

Results

High levels of TRAIL, CXCL12, and IL-1β were associated with an increased risk of NMOSD (TRAIL: odds ratio [OR], 1.582; 95% confidence interval [CI], 1.003–2.495; CXCL12: OR, 3.610; 95% CI, 1.011–12.889; IL-1β: OR, 4.500; 95% CI, 1.129–17.927). High levels of RvD1, MaR1, and LXA4 were associated with a reduced risk of NMOSD (RvD1: OR, 0.725; 95% CI, 0.538–0.976; MaR1: OR, 0.985; 95% CI, 0.970–0.999; LXA4: OR, 0.849; 95% CI, 0.727–0.993). Among patients with NMOSD, serum levels of IL-6, CXCL12, and TRAIL significantly decreased following IVMP treatment, compared with pretreatment levels, while levels of IL-1β, LXA4, and MaR1 significantly increased after IVMP treatment (p < 0.05). A significant positive correlation was observed between CXCL12 levels and Expanded Disability Status Scale (EDSS) scores (r = 0.451, p < 0.05).

Conclusion

Several systemic inflammatory regulators associated with the pathogenesis of NMOSD were identified. The protective roles of LXA4 and MaR1 may be indispensable components of glucocorticoid treatment. Therefore, the use of resolution markers may be a potential strategy for improving central nervous system injury in individuals with NMOSD.

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静脉注射脉冲甲基强的松龙对急性期神经脊髓炎视网膜病变的影响。

背景：神经脊髓炎视网膜谱系障碍（NMOSD）是一种由抗喹波蛋白4（anti-AQP4）自身抗体介导的中枢神经系统特发性炎症性脱髓鞘疾病。虽然静脉脉冲甲基强的松龙（IVMP）是急性发作的 NMOSD 的推荐初始治疗方案，但其治疗机制仍不清楚。我们假设 IVMP 将减少促炎因子的表达，并增加 NMOSD 患者炎症的缓解：方法：采用孟德尔随机化（MR）分析筛选有意义的炎症和缓解因子。主要使用三种带有反方差加权（IVW）的 MR 方法来确定阳性结果。从 41 个炎症因子中筛选出白细胞介素 (IL)-10、IL-1β、IL-6、C-X-C 矩阵趋化因子配体 12 (CXCL12)、肿瘤坏死因子相关凋亡诱导配体 (TRAIL)，从 6 个分辨率标记物中筛选出 resolvin D1 (RvD1)、maresin 1 (MaR1) 和 lipoxin A4 (LXA4)。随后，12 名 NMOSD 患者入选并接受了 IVMP 治疗。通过酶联免疫吸附试验测定了IVMP治疗前后血清中上述炎症标志物和溶解标志物的水平：结果：高水平的 TRAIL、CXCL12 和 IL-1β 与罹患 NMOSD 的风险增加相关（TRAIL：比值比 [OR]，1.582；95% 置信区间 [CI]，1.003-2.495；CXCL12：OR，3.610；95% CI，1.011-12.889；IL-1β：OR，4.500；95% CI，1.129-17.927）。高水平的 RvD1、MaR1 和 LXA4 与罹患 NMOSD 的风险降低有关（RvD1：OR，0.725；95% CI，0.538-0.976；MaR1：OR，0.985；95% CI，0.970-0.999；LXA4：OR，0.849；95% CI，0.727-0.993）。在 NMOSD 患者中，与治疗前相比，IL-6、CXCL12 和 TRAIL 的血清水平在 IVMP 治疗后显著降低，而 IL-1β、LXA4 和 MaR1 的水平在 IVMP 治疗后显著升高（p 结论：IL-6、CXCL12 和 TRAIL 的水平在 IVMP 治疗后显著降低，而 IL-1β、LXA4 和 MaR1 的水平在 IVMP 治疗后显著升高：研究发现了与 NMOSD 发病机制相关的几种全身炎症调节因子。LXA4 和 MaR1 的保护作用可能是糖皮质激素治疗不可或缺的组成部分。因此，使用分辨率标记物可能是改善 NMOSD 患者中枢神经系统损伤的潜在策略。

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来源期刊

Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)

CiteScore

9.10

自引率

1.90%

发文量

218

审稿时长

8 weeks

期刊介绍： Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.