Department of Neurology, Military Institute of Medicine, Warsaw, Poland.
Neuroimmunomodulation. 2013;20(4):213-22. doi: 10.1159/000348701. Epub 2013 May 24.
Interferon (IFN)β treatment is a mainstay of relapsing-remitting multiple sclerosis (RRMS) immunotherapy. Its efficacy is supposedly a consequence of impaired trafficking of inflammatory cells into the central nervous system and modification of the proinflammatory/antiinflammatory cytokine balance. However, the effects of long-term monotherapy using various IFNβ preparations on cytokine profiles and the relevance of these effects for the therapy outcome have not yet been elucidated.
Changes were compared in serum levels of TNFα, IFNγ, interleukin (IL)-6, IL-10 and nitrite between RRMS patients given 3-year treatment with intramuscular IFNβ-1a (30 μg once a week) or subcutaneous IFNβ-1b (250 μg every other day). Only the data from patients who completed the 3-year study (n = 20 and n = 18, respectively) were analyzed.
Three-year IFNβ-1a or IFNβ-1b monotherapy reduced serum nitrite levels by 77 and 71%, respectively, lowered multiple sclerosis relapse annual rate by 70 and 71%, respectively, and significantly and similarly lowered Expanded Disability Status Scale scores in both study groups (by 0.9 on average). The two monotherapies showed little if any effect on cytokine levels and cytokine level ratios after the first year, but exerted diverging effects on these indices later on; the only exception was the IFNγ/IL-6 ratio that showed a monotonous rise in both study groups over the entire study period.
During long-term IFNβ monotherapy, the levels of the studied cytokines show no relevance to the course of RRMS and neurological status of patients, whereas there seems to be a link between these clinical indices and the activity of nitric oxide-mediated pathways.
干扰素(IFN)β治疗是复发缓解型多发性硬化症(RRMS)免疫治疗的主要手段。其疗效据称是由于炎症细胞向中枢神经系统的运输受损以及促炎/抗炎细胞因子平衡的改变所致。然而,使用各种 IFNβ制剂进行长期单药治疗对细胞因子谱的影响,以及这些影响与治疗结果的相关性尚未阐明。
比较接受肌内 IFNβ-1a(每周一次 30μg)或皮下 IFNβ-1b(每隔一天 250μg)治疗 3 年的 RRMS 患者血清中 TNFα、IFNγ、白细胞介素(IL)-6、IL-10 和亚硝酸盐水平的变化。仅分析完成 3 年研究的患者(分别为 n=20 和 n=18)的数据。
3 年 IFNβ-1a 或 IFNβ-1b 单药治疗分别使血清亚硝酸盐水平降低 77%和 71%,分别使多发性硬化症年复发率降低 70%和 71%,并使两组患者的扩展残疾状况量表评分显著且相似地降低 0.9(平均)。两种单药治疗在第一年对细胞因子水平和细胞因子比值几乎没有影响,但随后对这些指标产生了不同的影响;唯一的例外是 IFNγ/IL-6 比值,在整个研究期间,两组患者的该比值均呈单调上升。
在长期 IFNβ单药治疗期间,研究细胞因子的水平与 RRMS 的病程和患者的神经状态无关,而这些临床指标与一氧化氮介导的途径的活性之间似乎存在联系。