Department of Neurology, Hannover Medical School, Hannover, Germany.
Mult Scler. 2011 Jul;17(7):851-66. doi: 10.1177/1352458511399797. Epub 2011 May 11.
In multiple sclerosis inflammation is primarily injurious to the central nervous system, but its therapeutic suppression might inhibit repair-promoting factors.
We aimed at better describing the complexity of biological effects during an acute relapse and analysed the effects of intervention with high-dose i.v. glucocorticoids and immunomodulatory treatment with interferon-beta (IFNβ).
We studied the intracellular expression levels of the pro-inflammatory mediators tumour necrosis factor alpha (TNFα) and inducible nitric oxide synthase (iNOS) together with the neurotrophins ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in freshly isolated peripheral blood mononuclear cells of multiple sclerosis patients during an acute relapse, after intervention with i.v. methylprednisolone and at baseline, using a highly quantitative flow-cytometric approach.
We demonstrated the expression of CNTF in human leucocytes. We showed that CNTF levels differed in acutely relapsing multiple sclerosis patients compared with controls and increased after corticosteroid treatment. CNTF can counteract the toxicity of TNFα towards oligodendrocytes and we found TNFα increased during acute relapses. Following corticosteroids, neither TNFα nor iNOS expression was reduced. Levels of BDNF were not affected by glucocorticoids, but increased during IFNβ therapy. However, IFNβ also increased the expression of iNOS and major histocompatibility complex class I (MHC-I), underlining its immunomodulatory potential.
Multiple sclerosis patients might benefit from reparative, and not solely from anti-inflammatory, effects of glucocorticoids. Interactive effects of glucocorticoid- and IFNβ-treatment need to be considered to improve neuroprotection and remyelination resulting from immunomodulatory treatment.
在多发性硬化症中，炎症主要对中枢神经系统造成伤害，但抑制其炎症反应可能会抑制修复促进因子。
我们旨在更好地描述急性复发期间的生物学效应的复杂性，并分析大剂量静脉内注射糖皮质激素和干扰素-β（IFNβ）免疫调节治疗的干预效果。
我们使用高度定量的流式细胞术方法，研究了急性复发期间多发性硬化症患者外周血单个核细胞中促炎介质肿瘤坏死因子-α（TNFα）和诱导型一氧化氮合酶（iNOS）的细胞内表达水平，以及神经营养因子睫状神经营养因子（CNTF）和脑源性神经营养因子（BDNF）的表达水平，然后进行了静脉内甲基强的松龙干预，并在基线时进行了研究。
我们证明了 CNTF 在人白细胞中的表达。我们表明，与对照组相比，急性复发多发性硬化症患者的 CNTF 水平不同，并且在皮质类固醇治疗后增加。CNTF 可以对抗 TNFα 对少突胶质细胞的毒性，我们发现 TNFα 在急性复发期间增加。皮质类固醇治疗后，TNFα 或 iNOS 的表达均未减少。BDNF 水平不受糖皮质激素的影响，但在 IFNβ 治疗期间增加。然而，IFNβ 还增加了主要组织相容性复合体 I（MHC-I）和 iNOS 的表达，强调了其免疫调节潜力。
多发性硬化症患者可能受益于糖皮质激素的修复作用，而不仅仅是抗炎作用。需要考虑糖皮质激素和 IFNβ 治疗的相互作用，以改善免疫调节治疗引起的神经保护和髓鞘再生。
