Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia.
School of Medicine, University of Tasmania, Hobart, Tasmania, Australia School of Pharmacy, University of Tasmania, Hobart, Tasmania, Australia.
J Neurol Neurosurg Psychiatry. 2015 Feb;86(2):200-7. doi: 10.1136/jnnp-2013-307336. Epub 2014 May 1.
Altered reactivity of peripheral blood mononuclear cells (PBMC) and their production of cytokines may affect multiple sclerosis (MS) clinical course. We assessed the relationship of stimulated PBMC-produced IFN-γ, TNF-α, IL-4 and IL-10 in modulating relapse risk using a prospective cohort with established relapsing-remitting MS.
Cytokine production from PBMCs taken in summer and winter was measured by ELISA. Predictors of cytokines assessed by multilevel mixed-effects linear regression. Predictors of relapse assessed by survival analysis.
Increasing IFN-γ was associated with increasing relapse risk, while increasing TNF-α reduced relapse risk after adjusting for IFN-γ. IL-10 and IL4 were not consistently associated with relapse risk. IFN-γ's effects on relapse were greatly attenuated by immunomodulatory therapies, by summer season and by higher serum vitamin D, whereas TNF-α's inverse association with relapse was only present in these circumstances. The TNF-α inverse association with relapse was only present among persons carrying the wild-type of the functional SNP rs1800693 in TNFRSF1A that has been previously associated with MS risk.
We found strong effects of IFN-γ and TNF-α on relapse risk, these differing by immunomodulatory therapy, season, and serum vitamin D, as well as by genotype. These results indicate altered reactivity of immune cells modulate MS disease.
外周血单个核细胞 (PBMC) 的反应性改变及其细胞因子的产生可能会影响多发性硬化症 (MS) 的临床病程。我们评估了使用已建立的复发缓解型 MS 的前瞻性队列，研究刺激 PBMC 产生的 IFN-γ、TNF-α、IL-4 和 IL-10 对调节复发风险的关系。
通过 ELISA 测量 PBMC 在夏季和冬季产生的细胞因子。使用多级混合效应线性回归来评估细胞因子的预测因子。通过生存分析评估复发的预测因子。
调整 IFN-γ 后，IFN-γ 增加与复发风险增加相关，而 TNF-α 增加则降低复发风险。IL-10 和 IL4 与复发风险没有一致的相关性。免疫调节治疗、夏季和较高的血清维生素 D 大大减弱了 IFN-γ 对复发的影响，而 TNF-α 与复发的反比关系仅在这些情况下存在。TNF-α 与复发的反比关系仅存在于 TNFRSF1A 中的功能性 SNP rs1800693 携带野生型的个体中，该 SNP 先前与 MS 风险相关。
我们发现 IFN-γ 和 TNF-α 对复发风险有很强的影响，这些影响因免疫调节治疗、季节和血清维生素 D 以及基因型而异。这些结果表明，免疫细胞的反应性改变调节了 MS 疾病。
