OBJECTIVES Clinically isolated syndrome (CIS) is the earliest clinical episode in multiple sclerosis (MS). A study of circulating cells from patients with CIS may help us understand the transition to, and processes associated with, the development of MS. METHODS As immune cell activity can be determined by flux through metabolic pathways, the mRNA expression of l-tryptophan- and l-arginine-catabolising enzymes, indoleamine 2,3-dioxygenase (IDO) 1 and IDO2 and arginase (ARG) 1 and ARG2, respectively, was compared between peripheral blood mononuclear cells (PBMCs) from healthy controls, and patients with CIS and definite MS. As one measure of cell function, cytokine mRNA levels were analysed directly ex vivo and in cells after culture for 4 h in the absence of regulatory factors in autologous serum. RESULTS When measured directly ex vivo, the expression of IDO and ARG was greater in cells from patients with CIS and MS than cells from healthy controls. Although not linked to IDO and ARG expression, PBMCs from the CIS patients were characterised by low IL-10 and TGFB mRNA levels and not by greater expression of proinflammatory cytokines. When the cells were cultured for 4 h without autologous serum, pro- and anti-inflammatory cytokine mRNA levels positively correlated with IDO1 expression, and TGFB mRNA levels correlated with ARG1 expression. CONCLUSION Higher IDO and ARG expression in CIS and MS provides one sustained homeostatic mechanism to control MS-associated inflammation. However, potent extrinsic mediators in serum may regulate immune cell function in CIS and associations between IDO, ARG and cytokine expression.

中文翻译：

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临床孤立综合征和多发性硬化症中的色氨酸和精​​氨酸分解代谢酶和调节细胞因子。

目的 临床孤立综合征 (CIS) 是多发性硬化症 (MS) 中最早的临床发作。对 CIS 患者循环细胞的研究可能有助于我们了解 MS 向 MS 发展的转变和相关过程。方法 由于免疫细胞活性可以​​通过代谢途径的通量、l-色氨酸和 l-精氨酸分解代谢酶、吲哚胺 2,3-双加氧酶 (IDO) 1 和 IDO2 以及精氨酸酶 (ARG) 1 和 ARG2 的 mRNA 表达来确定分别比较了来自健康对照的外周血单个核细胞 (PBMC) 与患有 CIS 和确诊 MS 的患者。作为细胞功能的一种测量方法，在自体血清中不存在调节因子的情况下，在培养 4 小时后直接离体和在细胞中分析细胞因子 mRNA 水平。结果 当直接离体测量时，CIS 和 MS 患者细胞中 IDO 和 ARG 的表达高于健康对照细胞。尽管与 IDO 和 ARG 表达无关，但来自 CIS 患者的 PBMC 的特征是低 IL-10 和 TGFB mRNA 水平，而不是促炎细胞因子的更多表达。当细胞在没有自体血清的情况下培养4小时时，促炎和抗炎细胞因子mRNA水平与IDO1表达呈正相关，TGFB mRNA水平与ARG1表达相关。结论 CIS 和 MS 中较高的 IDO 和 ARG 表达为控制 MS 相关炎症提供了一种持续的稳态机制。然而，血清中有效的外在介质可以调节 CIS 中的免疫细胞功能以及 IDO、ARG 和细胞因子表达之间的关联。