Glucocorticoids increase IL-10 expression in multiple sclerosis patients with acute relapse
Glucocorticoids increase IL-10 expression in multiple sclerosis patients with acute relapse
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DOI：
10.1016/s0165-5728(97)00262-2
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发表时间：
1998-05-15
影响因子：
3.3
通讯作者：
Gutiérrez, C
中科院分区：
文献类型：
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作者：
Gayo, A;Mozo, L;Gutiérrez, C
高剂量糖皮质激素（GCs）被广泛用于治疗复发缓解型多发性硬化症（MS）患者的急性发作。它们的有益作用部分是由于它们调节细胞因子网络的能力。在目前的工作中，我们研究了GCs对免疫抑制细胞因子IL-10产生的影响。在开始治疗前和接受每日1g静脉注射甲基强的松龙（MP）四天后，立即采集急性复发的MS患者的血液样本。RT-PCR半定量检测PBMC中IL-10 mRNA水平，ELISA检测血清和细胞培养上清蛋白浓度。我们的研究结果显示，9例患者中有7例IL-10 mRNA表达增加，并且；类固醇治疗后血清IL-10浓度升高。相反，两种炎症细胞因子TNF α和IFN γ的mRNA表达在类固醇治疗后下降。体外正常PBMC实验表明，甲基强的松龙（methylprednisolone， MP）上调IL-10的表达，通过测定mRNA水平、流式细胞术检测胞浆内蛋白浓度和分泌蛋白量来确定。经MP处理的PBMC培养细胞分泌的IL-10在48小时达到峰值。当糖皮质激素受体拮抗剂RU486存在时，IL-10的表达逆转到基线水平，这种效果是类固醇特异性的。与MP对IL-10自发表达的影响相反，该药物下调了lps诱导的IL-10合成。事实上，在细胞培养中加入MP后，lps诱导的正常PBMC分泌IL-10的IL-10浓度降低。因此，MP似乎对自发和lps诱导的IL-10产生相反的作用。我们的研究表明，GCs可能通过上调免疫抑制细胞因子IL-10的产生来控制炎症反应。(C) 1998 Elsevier Science B.V.版权所有
High doses of glucocorticoids (GCs) are widely employed to treat acute attacks in relapsing-remitting multiple sclerosis (MS) patients. Their beneficial effects are partially due to their capacity to regulate the cytokine network. In the present work, we have examined the effect of GCs on the production of the immunosuppressor cytokine IL-10. Blood samples from MS patients suffering an acute relapse were obtained immediately before initiating therapy and after receiving a daily dose of 1 g intravenous methylprednisolone (MP) for four days. Levels of IL-10 mRNA in PBMC were semiquantified by RT-PCR, whereas protein concentration in serum and in cell culture supernatant was measured by ELISA. Our results show that 7 out of the 9 patients studied displayed increased IL-10 mRNA expression as well as;higher serum IL-10 concentration following steroid treatment. In contrast, mRNA expression of two inflammatory cytokines, TNF alpha and IFN gamma, decreased following steroid therapy. In vitro experiments employing normal PBMC showed that methylprednisolone (MP) upregulated IL-10 expression as determined by measuring mRNA levels, flow cytometry of intracytoplasmic protein concentration, and the amount of secreted protein. Peak responses of secreted IL-10 by PBMC cultured cells treated with MP were obtained at 48 h. The effect was steroid-specific as IL-10 expression reversed to baseline levels in the presence of the glucocorticoid receptor antagonist RU486. Contrary to the effect of MP on the spontaneous expression of IL-10, this drug downregulated LPS-induced IL-10 synthesis. In fact, the concentration of IL-10 in LPS-induced IL-10 secretion from normal PBMC decreased upon addition of MP to cell cultures. Thus, it seems that MP exerts an opposite effect on the spontaneous and LPS-induced IL-10 production. Our studies indicate that GCs may control inflammatory responses by upregulating production of the immunosuppressor cytokine IL-10. (C) 1998 Elsevier Science B.V. All rights reserved.