PMID- 29063487 OWN - NLM STAT- MEDLINE DCOM- 20180808 LR - 20181113 IS - 1568-5608 (Electronic) IS - 0925-4692 (Linking) VI - 26 IP - 1 DP - 2018 Feb TI - Targeting of circulating Th17 cells by beta-D-mannuronic acid (M2000) as a novel medication in patients with rheumatoid arthritis. PG - 57-65 LID - 10.1007/s10787-017-0410-8 [doi] AB - OBJECTIVE: This study aimed at investigating the inhibitory effect of beta-D-mannuronic acid (M2000) on the Th17 circulating levels and IL-17 a related cytokine in rheumatoid arthritis (RA) patients. METHODS: 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 (TNFalpha) 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. RESULTS: 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). CONCLUSION: M2000 shows the inhibitory effect on the frequency of circulating Th17 cells as well as in the production of IL-17 in RA patients. FAU - Ahmadi, Hossein AU - Ahmadi H AD - Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Box: 14155-6446, Tehran, Iran. FAU - Mahmoudi, Mahdi AU - Mahmoudi M AD - Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. FAU - Gharibdoost, Farhad AU - Gharibdoost F AD - Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. FAU - Vojdanian, Mahdi AU - Vojdanian M AD - Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. FAU - Jamshidi, Ahmad Reza AU - Jamshidi AR AD - Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. FAU - Fattahi, Mohammad Javad AU - Fattahi MJ AD - Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Box: 14155-6446, Tehran, Iran. AD - Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. FAU - Aghazadeh, Zahra AU - Aghazadeh Z AD - Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Box: 14155-6446, Tehran, Iran. FAU - Barati, Anis AU - Barati A AD - Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Box: 14155-6446, Tehran, Iran. FAU - Mirshafiey, Abbas AU - Mirshafiey A AD - Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Box: 14155-6446, Tehran, Iran. mirshafiey@tums.ac.ir. LA - eng PT - Clinical Trial PT - Journal Article DEP - 20171023 PL - Switzerland TA - Inflammopharmacology JT - Inflammopharmacology JID - 9112626 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Antirheumatic Agents) RN - 0 (Cytokines) RN - 0 (Hexuronic Acids) RN - 0 (Interleukin-17) RN - 0 (Tumor Necrosis Factor-alpha) RN - 980IT47Y34 (mannuronic acid) RN - OP401G7OJC (Etanercept) SB - IM MH - Adult MH - Aged MH - Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use MH - Antirheumatic Agents/*therapeutic use MH - Arthritis, Rheumatoid/*drug therapy/metabolism MH - Case-Control Studies MH - Cytokines/metabolism MH - Etanercept/therapeutic use MH - Female MH - Hexuronic Acids/*therapeutic use MH - Humans MH - Interleukin-17/blood MH - Male MH - Middle Aged MH - Th17 Cells/*drug effects/*metabolism MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - DMARD OT - IL-17 OT - M2000 OT - Mannuronic acid OT - Rheumatoid arthritis OT - Th17 cells EDAT- 2017/10/25 06:00 MHDA- 2018/08/09 06:00 CRDT- 2017/10/25 06:00 PHST- 2017/09/04 00:00 [received] PHST- 2017/10/11 00:00 [accepted] PHST- 2017/10/25 06:00 [pubmed] PHST- 2018/08/09 06:00 [medline] PHST- 2017/10/25 06:00 [entrez] AID - 10.1007/s10787-017-0410-8 [pii] AID - 10.1007/s10787-017-0410-8 [doi] PST - ppublish SO - Inflammopharmacology. 2018 Feb;26(1):57-65. doi: 10.1007/s10787-017-0410-8. Epub 2017 Oct 23.