Afraei Sanaz, Sedaghat Reza, Zavareh Farzaneh Tofighi, Aghazadeh Zahra, Ekhtiari Parvin, Azizi Gholamreza, Mirshafiey Abbas
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Department of Anatomy and Pathology, Faculty of Medicine, Shahed University, Tehran, Iran.
Cent Eur J Immunol. 2018;43(1):9-17. doi: 10.5114/ceji.2018.74868. Epub 2018 Mar 30.
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS). EAE is mainly mediated by adaptive and innate immune responses that lead to an inflammatory demyelination and axonal damage. The aim of the present research was to examine the therapeutic efficacy of Peg interferon alpha 2a (Peg-IFN α-2a) as a serine protease inhibitor on EAE model.
EAE induction was performed in female C57BL/6 mice by myelin oligodendrocyte glycoprotein (35-55) (MOG) in Complete Freund's Adjuvant (CFA) emulsion, and Peg-IFN α-2a was used for the treatment of EAE. During the course of the study, clinical evaluation was assessed, and on day 21 post-immunisation blood samples were taken from the heart of mice for evaluation of IL-6, and enzymatic and non-enzymatic antioxidants. The mice were sacrificed and the brains and cerebellums were removed for histological analysis.
Our findings indicated that Peg-IFN α-2a had beneficial effects on EAE by attenuation of the severity and a delay in the onset of disease. Histological analysis showed that treatment with Peg-IFN α-2a can reduce inflammation criteria. Moreover, in Peg-IFN α-2a-treated mice the serum level of IL-6 was significantly less than in controls, and total antioxidant capacity was significantly more than in the control animals.
These data indicate that Peg-IFN α-2a as an anti-serine protease with immunomodulatory properties may be useful for the treatment of MS.
实验性自身免疫性脑脊髓炎(EAE)是多发性硬化症(MS)的动物模型。EAE主要由适应性和先天性免疫反应介导,导致炎症性脱髓鞘和轴突损伤。本研究的目的是检验聚乙二醇化干扰素α-2a(Peg-IFNα-2a)作为丝氨酸蛋白酶抑制剂对EAE模型的治疗效果。
通过在完全弗氏佐剂(CFA)乳剂中注射髓鞘少突胶质细胞糖蛋白(35-55)(MOG),在雌性C57BL/6小鼠中诱导EAE,并使用Peg-IFNα-2a治疗EAE。在研究过程中,进行临床评估,并在免疫后第21天从小鼠心脏采集血样,以评估白细胞介素-6、酶促和非酶促抗氧化剂。处死小鼠,取出大脑和小脑进行组织学分析。
我们的研究结果表明,Peg-IFNα-2a通过减轻疾病严重程度和延迟疾病发作对EAE有有益作用。组织学分析表明,Peg-IFNα-2a治疗可降低炎症指标。此外,在接受Peg-IFNα-2a治疗的小鼠中,白细胞介素-6的血清水平显著低于对照组,总抗氧化能力显著高于对照动物。
这些数据表明,Peg-IFNα-2a作为一种具有免疫调节特性的抗丝氨酸蛋白酶,可能对MS的治疗有用。