Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Box: 14155-6446, Tehran, Iran.
Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Inflammopharmacology. 2018 Feb;26(1):57-65. doi: 10.1007/s10787-017-0410-8. Epub 2017 Oct 23.
This study aimed at investigating the inhibitory effect of β-D-mannuronic acid (M2000) on the Th17 circulating levels and IL-17 a related cytokine in rheumatoid arthritis (RA) patients.
The study included 27 patients with RA who had failed response to treatment. All patients were treated orally by M2000 at a dose of 500 mg twice daily for 12 weeks (Clinical trial identifier: IRCT2014011213739N2). The patients based on anti-tumor necrosis factor alpha (TNFα) blocker treatment were classified into two groups (conventional group and etanercept group). They were then allowed to continue their treatment excluding non-steroidal anti-inflammatory drugs (NSAIDs). The frequency of circulating Th17 cells and IL-17 serum level were determined before and 12 weeks after M2000 therapy and were compared to the healthy controls by using flow cytometry analysis and ELISA method, respectively.
At baseline, higher circulating Th17 and IL-17 serum levels were significantly observed in both groups of RA patients than in the healthy controls (all P < 0.001). The frequency of Th17 cells significantly decreased in the conventional group as well as in the etanercept group after M2000 therapy but the level of reduction was higher in the conventional group compared to the etanercept group (P < 0.03 and P < 0.04, respectively). The IL-17 serum level significantly decreased in both groups after M2000 therapy (P < 0.01 and P < 0.02, respectively). Furthermore, the frequency of Th17 cells was positively correlated with Disease Activity Score (DAS28) (r = 0.34, P = 0.02).
M2000 shows the inhibitory effect on the frequency of circulating Th17 cells as well as in the production of IL-17 in RA patients.
本研究旨在探讨β-D-甘露糖醛酸（M2000）对类风湿关节炎（RA）患者循环 Th17 水平及相关细胞因子 IL-17 的抑制作用。
本研究纳入 27 例治疗反应不佳的 RA 患者。所有患者均口服 M2000，剂量为 500mg，每日两次，疗程 12 周（临床试验标识符：IRCT2014011213739N2）。根据抗肿瘤坏死因子-α（TNFα）阻滞剂治疗，患者分为两组（常规组和依那西普组）。然后，允许他们继续治疗，但不包括非甾体抗炎药（NSAIDs）。采用流式细胞术分析和 ELISA 法分别检测 M2000 治疗前后循环 Th17 细胞频率和 IL-17 血清水平，并与健康对照组比较。
基线时，两组 RA 患者的循环 Th17 和 IL-17 血清水平均明显高于健康对照组（均 P<0.001）。M2000 治疗后，常规组和依那西普组 Th17 细胞频率均显著降低，但常规组降低幅度高于依那西普组（分别为 P<0.03 和 P<0.04）。两组患者 M2000 治疗后 IL-17 血清水平均显著降低（分别为 P<0.01 和 P<0.02）。此外，Th17 细胞频率与疾病活动评分（DAS28）呈正相关（r=0.34，P=0.02）。
M2000 对 RA 患者循环 Th17 细胞频率及 IL-17 产生具有抑制作用。
