干扰素β-1b对实验性自身免疫性脑脊髓炎脊髓中趋化因子MCP-1表达的影响

Effect of interferon β-1b on chemokine MCP-1 expression in spinal cord of EAE mice

目的研究干扰素（IFN）β-1b对实验性自身免疫性脑脊髓炎（EAE）小鼠中枢神经系统（CNS）中单核细胞趋化蛋白-1（MCP-1）表达的影响，从趋化因子角度探讨IFNβ治疗多发性硬化（MS）的机制。方法用髓鞘少突胶质细胞糖蛋白35～55多肽加福氏完全佐剂皮下注射免疫C57BL／6小鼠建立EAE模型，干预组（n=12）在免疫当天至免疫后第16天隔日一次皮下注射10000单位IFNβ-1b，对照组（n=12）则同时予1mL PBS皮下注射。比较两组EAE小鼠的临床表现，并用免疫组织化学及原位杂交技术比较两组EAE脊髓中MCP-1表达及MCP-1mRNA水平的差异。结果与对照组相比，IFNβ-1b干预组小鼠发病明显延迟，症状明显减轻，同时脊髓中MCP-1的表达及MCP-1mRNA的水平显著下调。结论IFNβ-1b可抑制EAE小鼠CNS中趋化因子MCP-1的表达，这可能是其治疗MS的机制之一。

Objective To understand the mechanism underlying the beneficial effect of interferon （IFN） β on multiple sclerosis （MS） by investigating the effect oflFN β-1b on monocyte chemoattraetant protein （MCP）-1 expression in the central nervous system （CNS） of experimental autoimmune encephalomyelitis （EAE） mice. Methods EAE models in C57BL/6 mice were induced by injecting subcutaneously myelin oligodendrocyte glycoprotein 35-55 peptide in complete Freund＇s adjuvant. One group （n=12） were treated by injecting subcutaneously 1 mL recombinant human IFN β-1b at 10 000 units on alternate days from the day of EAE modeling to day 16, and the other group （n=12） were injected subcutaneously with 1 mL PBS at the same time. We compared the clinical symptoms between the 2 groups. The differences of MCP-1 expression and MCP-1 mRNA level in the spinal cord between the 2 groups were also compared by immunohistochemistry and in situ hybridization. Results IFN β-1b reduced the disease activity, significantly decreased MCP-1 expression and down-regulated MCP-1 mRNA level in the spinal cord of EAE mice. Conclusion IFN β-1b treatment decreased the expression of MCP-1 in EAE lesions, which may be one of the regulatory mechanisms of IFN β for the treatment of MS.