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阿沃尼单抗在复发缓解型多发性硬化症患者中的复杂作用机制:白细胞介素-17A、白细胞介素-10和转化生长因子-β血清滴度的变化

An Intricate Mechanism of Action of Avonex in Relapsing Remitting Multiple Sclerosis Patients: Variation of Serum Titre of Interleukin-17A, Interleukin-10 and Transforming Growth Factor-β.

作者信息

Balasa Rodica, Maier Smaranda, Voidazan Septimiu, Hutanu Adina, Bajko Zoltan, Motataianu Anca

机构信息

First Neurological Clinic, University Emergency County Hospital Targu Mures, Gh Marinescu Street 50, Mures County, Romania.

出版信息

CNS Neurol Disord Drug Targets. 2015;14(6):804-10. doi: 10.2174/1871527314666150317225441.

Abstract

INTRODUCTION

The immunopathogenesis of multiple sclerosis (MS) is a main field of research, together with the mechanism of action of most immune therapies in this disease, such as interferon beta. Interleukin (IL)-17 is considered to play a central part in the initial immune cascade in MS, though there are numerous interactions between other cytokines that might explain the heterogeneity of disease evolution and treatment response.

MATERIAL AND METHODS

We tested the serum levels of IL-17A, IL-10 and transforming growth factor (TGF-β) using the enzyme-linked immunosorbent assay method in three small groups of relapsing-remitting MS patients: 10 being naïve without treatment, 10 patients receiving Avonex treatment early in the MS evolution (≤ one year from the MS onset) and 12 MS patients who received Avonex later in the disease evolution. The values were compared with those obtained from 32 healthy subjects using statistical analysis.

RESULTS

In the naive multiple sclerosis group: IL-17A values were statistically higher than among healthy subjects; IL- 17A inversely correlated with MS duration; serum IL-17A negatively correlated with TGF-β. A direct correlation was found between the serum titre of IL-17A and IL-10 in the early treated multiple sclerosis group; the titre of IL-17A was significantly reduced compared with that from the late treated multiple sclerosis group.

CONCLUSION

The role in MS pathology of IL-17A, IL-10 and TGF-β is only partially elucidated. IL-17 plays an important role in the inflammatory phase of relapsing-remitting MS and is diminished by Avonex mainly if this disease modifying treatment is administered early in the evolution of MS.

摘要

引言

多发性硬化症(MS)的免疫发病机制是一个主要的研究领域,同时也是大多数免疫疗法(如干扰素β)在该疾病中的作用机制的研究领域。白细胞介素(IL)-17被认为在MS的初始免疫级联反应中起核心作用,尽管其他细胞因子之间存在众多相互作用,这可能解释了疾病演变和治疗反应的异质性。

材料与方法

我们采用酶联免疫吸附测定法检测了三组复发缓解型MS患者血清中IL-17A、IL-10和转化生长因子(TGF-β)的水平:10例未经治疗的初发患者,10例在MS病程早期(发病≤1年)接受阿沃尼单抗治疗的患者,以及12例在疾病病程后期接受阿沃尼单抗治疗的MS患者。使用统计分析将这些值与32名健康受试者的值进行比较。

结果

在未经治疗的多发性硬化症组中:IL-17A值在统计学上高于健康受试者;IL-17A与MS病程呈负相关;血清IL-17A与TGF-β呈负相关。在早期治疗的多发性硬化症组中,发现IL-17A血清滴度与IL-10之间存在直接相关性;与后期治疗的多发性硬化症组相比,IL-17A滴度显著降低。

结论

IL-17A、IL-10和TGF-β在MS病理中的作用仅得到部分阐明。IL-17在复发缓解型MS的炎症阶段起重要作用,并且如果这种疾病修饰治疗在MS病程早期给予,阿沃尼单抗可使其降低。

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