van Boxel-Dezaire A H, van Trigt-Hoff S C, Killestein J, Schrijver H M, van Houwelingen J C, Polman C H, Nagelkerken L
Division of Immunological and Infectious Diseases, TNO Prevention of Health, Leiden University Medical Center, The Netherlands.
Ann Neurol. 2000 Sep;48(3):313-22. doi: 10.1002/1531-8249(200009)48:3<313::aid-ana5>3.3.co;2-0.
Interferon (IFN)-beta treatment is effective in relapsing-remitting multiple sclerosis (RR-MS) via an as yet unidentified mechanism. In the present study, we investigated whether the expression of messenger RNA (mRNA) encoding the interleukin (IL)-12 subunits p40 and p35, IL-12 receptor chains, IL-18, tumor necrosis factor-alpha (TNFalpha), IFNgamma, IL-10, IL-4, or transforming growth factor-beta in unstimulated whole blood of 26 RR-MS patients changed during 6 months of IFNbeta-1b treatment. In these patients, a significant change was found in TNFalpha mRNA, whereas changes in IL-12 receptor-beta2 and IL-10 mRNA showed a trend. IFNbeta-1b-related changes in cytokine mRNA expression were next evaluated in clinical subgroups of RR-MS patients classified as either clinical responders or nonresponders on the basis of Expanded Disability Status Scale progression and the number of relapses and steroid interventions needed in the 2 years before initiation of treatment compared with the 2 years after initiation of treatment. These subgroups showed different response patterns to IFNbeta-1b treatment with respect to IL-10, TNFalpha, and IL-18 only. Surprisingly, clinical responders displayed no change in these cytokines, whereas nonresponders showed a decrease in TNFalpha and IL-18 mRNA as well as a transient increase in IL-10 mRNA. Baseline levels of IL-12p35 mRNA were lower in the responders compared with the nonresponders: this marker correctly predicted the clinical outcome in 81% of the 26 patients under investigation.
干扰素(IFN)-β治疗通过一种尚未明确的机制对复发缓解型多发性硬化症(RR-MS)有效。在本研究中,我们调查了26例RR-MS患者未经刺激的全血中编码白细胞介素(IL)-12亚基p40和p35、IL-12受体链、IL-18、肿瘤坏死因子-α(TNFα)、IFNγ、IL-10、IL-4或转化生长因子-β的信使核糖核酸(mRNA)表达在IFNβ-1b治疗6个月期间是否发生变化。在这些患者中,发现TNFα mRNA有显著变化,而IL-12受体-β2和IL-10 mRNA的变化呈趋势性。接下来,根据扩展残疾状态量表进展以及治疗开始前2年与治疗开始后2年所需的复发次数和类固醇干预情况,将RR-MS患者分为临床反应者或无反应者临床亚组,评估IFNβ-1b相关的细胞因子mRNA表达变化。这些亚组仅在IL-10、TNFα和IL-18方面对IFNβ-1b治疗表现出不同的反应模式。令人惊讶的是,临床反应者这些细胞因子无变化,而无反应者TNFα和IL-18 mRNA下降,IL-10 mRNA短暂升高。反应者的IL-12p35 mRNA基线水平低于无反应者:该标志物在26例受调查患者中有81%正确预测了临床结果。