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褪黑素与干扰素-β和那他珠单抗免疫调节疗法治疗多发性硬化症小鼠模型的比较研究。

A comparative study of melatonin and immunomodulatory therapy with interferon beta and glatiramer acetate in a mouse model of multiple sclerosis.

机构信息

Departamento de Fisiología, Centro Universitario Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México; División de Neurociencias, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.

División de Neurociencias, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.

出版信息

Neurologia (Engl Ed). 2021 May;36(4):262-270. doi: 10.1016/j.nrl.2018.01.007. Epub 2018 Mar 9.

Abstract

INTRODUCTION

Multiple sclerosis (MS) is a chronic, demyelinating, autoimmune disease of the central nervous system causing neuroinflammation. Experimental autoimmune encephalitis (EAE) is a model of the disease. MS is classically treated with interferon beta (IFN-β) and glatiramer acetate (GA). Melatonin (MLT) has been reported to modulate immune system responses. The aim of the present study is to analyse the effects of MLT administration in comparison with the first-line treatments for MS (IFN-β and GA).

METHODS

EAE was induced in male Sprague-Dawley rats; the animals subsequently received either IFN-β, GA, or MLT. Cerebrospinal fluid (CSF) samples were analysed by multiplex assay to determine the levels of proinflammatory cytokines. The neurological evaluation of EAE was also recorded.

RESULTS

All immunised animals developed EAE. We evaluated the first relapse-remission cycle, observing that IFN-β and GA had better results than MLT in the clinical evaluation. Neither EAE nor any of the treatments administered modified CSF IL-1β and IL-12p70 concentrations. However, IFN-β and MLT did decrease CSF TNF-α concentrations.

CONCLUSIONS

Further studies are needed to evaluate the molecular mechanisms involved in the behaviour of MLT in EAE, and to quantify other cytokines in different biological media in order for MLT to be considered an anti-inflammatory agent capable of regulating MS.

摘要

简介

多发性硬化症(MS)是一种中枢神经系统的慢性脱髓鞘自身免疫性疾病,可导致神经炎症。实验性自身免疫性脑脊髓炎(EAE)是该病的模型。MS 经典的治疗方法是使用干扰素β(IFN-β)和醋酸格拉替雷(GA)。褪黑素(MLT)已被报道可调节免疫系统反应。本研究旨在分析 MLT 给药与 MS 的一线治疗(IFN-β 和 GA)相比的效果。

方法

雄性 Sprague-Dawley 大鼠诱导 EAE;随后,动物接受 IFN-β、GA 或 MLT 治疗。通过多重分析测定脑脊液(CSF)样本中促炎细胞因子的水平。还记录 EAE 的神经学评估。

结果

所有免疫的动物都发生了 EAE。我们评估了第一个复发缓解周期,观察到 IFN-β 和 GA 在临床评估中的效果优于 MLT。EAE 或任何给予的治疗均未改变 CSF IL-1β 和 IL-12p70 浓度。然而,IFN-β 和 MLT 确实降低了 CSF TNF-α 浓度。

结论

需要进一步研究以评估 MLT 在 EAE 中的作用的分子机制,并在不同的生物介质中定量其他细胞因子,以便将 MLT 视为一种具有调节 MS 能力的抗炎剂。

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