干扰素β-1b治疗可调节多发性硬化症中肿瘤坏死因子α和干扰素γ的自发基因表达。

Interferon beta-1b treatment modulates TNFalpha and IFNgamma spontaneous gene expression in MS.

作者信息

Gayo A, Mozo L, Suárez A, Tuñón A, Lahoz C, Gutiérrez C

机构信息

Department of Immunology, Hospital Central de Asturias, Universidad de Oviedo, Spain.

出版信息

Neurology. 1999 Jun 10;52(9):1764-70. doi: 10.1212/wnl.52.9.1764.

DOI:10.1212/wnl.52.9.1764

PMID:10371521

Abstract

BACKGROUND

Interferon beta (IFNbeta) lessens the overall frequency of acute attacks in patients with the relapsing-remitting form of multiple sclerosis (RRMS). IFNbeta may act by decreasing the synthesis of inflammatory cytokines.

OBJECTIVES

To determine whether IFNbeta-1b treatment had an initial and sustained effect on the in vivo synthesis and secretion of tumor necrosis factor alpha (TNFalpha) and IFNgamma.

METHODS

A highly sensitive reverse-transcriptase PCR technique was used to measure baseline levels of mRNA in freshly isolated cells from patients before therapy and at 3, 6, and 12 months of treatment. Also, protein concentration was measured in serum and in culture supernatants from mitogen-stimulated cells. The authors studied 16 patients, of whom 11 did not have clinical exacerbations, whereas 5 had one clinical relapse each during the study.

RESULTS

Mean values of TNFalpha mRNA levels in the 11 stable patients decreased significantly at 3 and 6 months of treatment in comparison with initial data. After 6 months of therapy, IFNbeta-1b downmodulated TNFalpha transcripts in the 5 patients who experienced relapse. In this group of patients, TNFalpha levels rose sharply to reach pretreated values at 1 year of IFNbeta-1b treatment. At the beginning of therapy, 6 patients had high concentrations of serum TNFalpha, which decreased to normal values following IFNbeta-1b therapy. IFNgamma mRNA expression also diminished after 6 and 12 months of IFNbeta-1b therapy in the group of stable patients, whereas nonrelevant variations were observed in patients who had one relapse. Initially, patients' peripheral mononuclear cells secreted diminished amounts of TNFalpha and IFNgamma on PHA + PMA mitogen stimulation in comparison with normal control subjects. After 1 year of therapy, IFNbeta-1b restored the normal production of TNFalpha, whereas therapy did not restore IFNgamma secretion to control values.

CONCLUSION

IFNbeta-1b decreases the spontaneous expression of two proinflammatory cytokines.

摘要

背景

干扰素β（IFNβ）可降低复发缓解型多发性硬化症（RRMS）患者急性发作的总体频率。IFNβ可能通过减少炎性细胞因子的合成发挥作用。

目的

确定IFNβ-1b治疗对肿瘤坏死因子α（TNFα）和干扰素γ（IFNγ）的体内合成及分泌是否具有初始和持续影响。

方法

采用高灵敏度逆转录聚合酶链反应技术，测量治疗前及治疗3、6和12个月时患者新鲜分离细胞中mRNA的基线水平。此外，还测量了丝裂原刺激细胞的血清及培养上清液中的蛋白质浓度。作者研究了16例患者，其中11例无临床病情加重，而5例在研究期间各有一次临床复发。

结果

与初始数据相比，11例病情稳定患者的TNFα mRNA水平平均值在治疗3个月和6个月时显著降低。治疗6个月后，IFNβ-1b使5例复发患者的TNFα转录本下调。在这组患者中，TNFα水平在IFNβ-1b治疗1年时急剧上升至治疗前水平。治疗开始时，6例患者血清TNFα浓度较高，IFNβ-1b治疗后降至正常水平。在病情稳定的患者组中，IFNβ-1b治疗6个月和12个月后，IFNγ mRNA表达也降低，而有一次复发的患者中观察到无显著变化。最初，与正常对照受试者相比，患者外周血单个核细胞在PHA + PMA丝裂原刺激下分泌的TNFα和IFNγ量减少。治疗1年后，IFNβ-1b恢复了TNFα的正常产生，而治疗未将IFNγ分泌恢复至对照值。