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Erschienen in: Inflammopharmacology 1/2018

23.10.2017 | Original Article

Targeting of circulating Th17 cells by β-D-mannuronic acid (M2000) as a novel medication in patients with rheumatoid arthritis

verfasst von: Hossein Ahmadi, Mahdi Mahmoudi, Farhad Gharibdoost, Mahdi Vojdanian, Ahmad reza Jamshidi, Mohammad javad Fattahi, Zahra Aghazadeh, Anis Barati, Abbas Mirshafiey

Erschienen in: Inflammopharmacology | Ausgabe 1/2018

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Abstract

Objective

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.

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 (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.

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.
Literatur
Zurück zum Zitat Ahmadi H, Jamshidi A, Mahmoudi M et al (2017) The potent inhibitory effect of β-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property on anti-cyclic citrullinated peptide antibodies, rheumatoid factor and anti-dsDNA antibodies in patients with rheumatoid arthritis. Curr Drug Discov Technol 14(3):206–214. doi:10.2174/1570163814666170321113059 CrossRefPubMed Ahmadi H, Jamshidi A, Mahmoudi M et al (2017) The potent inhibitory effect of β-D-mannuronic acid (M2000) as a novel NSAID with immunosuppressive property on anti-cyclic citrullinated peptide antibodies, rheumatoid factor and anti-dsDNA antibodies in patients with rheumatoid arthritis. Curr Drug Discov Technol 14(3):206–214. doi:10.​2174/​1570163814666170​321113059 CrossRefPubMed
Zurück zum Zitat Aletaha D, Neogi T, Silman AJ et al (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League against rheumatism collaborative initiative. Arth Rheumatol 62:2569–2581CrossRef Aletaha D, Neogi T, Silman AJ et al (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League against rheumatism collaborative initiative. Arth Rheumatol 62:2569–2581CrossRef
Zurück zum Zitat Alzabin S, Abraham SM, Taher TE et al (2012) Incomplete response of inflammatory arthritis to TNFα blockade is associated with the Th17 pathway. Ann Rheum Dis 71:1741–1748CrossRefPubMed Alzabin S, Abraham SM, Taher TE et al (2012) Incomplete response of inflammatory arthritis to TNFα blockade is associated with the Th17 pathway. Ann Rheum Dis 71:1741–1748CrossRefPubMed
Zurück zum Zitat Astry B, Harberts E, Moudgil KD (2011) A cytokine-centric view of the pathogenesis and treatment of autoimmune arthritis. J Interferon Cytokine Res 31:927–940CrossRefPubMedPubMedCentral Astry B, Harberts E, Moudgil KD (2011) A cytokine-centric view of the pathogenesis and treatment of autoimmune arthritis. J Interferon Cytokine Res 31:927–940CrossRefPubMedPubMedCentral
Zurück zum Zitat Barati A, Jamshidi AR, Ahmadi H et al (2017) Effects of β-d-mannuronic acid, as a novel non-steroidal anti-inflammatory medication within immunosuppressive properties, on IL17, RORγt, IL4 and GATA3 gene expressions in rheumatoid arthritis patients. Drug Des Dev 11:1027CrossRef Barati A, Jamshidi AR, Ahmadi H et al (2017) Effects of β-d-mannuronic acid, as a novel non-steroidal anti-inflammatory medication within immunosuppressive properties, on IL17, RORγt, IL4 and GATA3 gene expressions in rheumatoid arthritis patients. Drug Des Dev 11:1027CrossRef
Zurück zum Zitat Beringer A, Noack M, Miossec P (2016) IL-17 in chronic inflammation: from discovery to targeting. Trends Mol Med 22:230–241CrossRefPubMed Beringer A, Noack M, Miossec P (2016) IL-17 in chronic inflammation: from discovery to targeting. Trends Mol Med 22:230–241CrossRefPubMed
Zurück zum Zitat Fattahi MJ, Abdollahi M, Mohammadi Agha et al (2015) Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug. Immunopharmacol Immunotoxicol 37:535–540CrossRefPubMed Fattahi MJ, Abdollahi M, Mohammadi Agha et al (2015) Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug. Immunopharmacol Immunotoxicol 37:535–540CrossRefPubMed
Zurück zum Zitat Firestein GS, McInnes IB (2017) Immunopathogenesis of rheumatoid arthritis. Immunity 46:183–196CrossRefPubMed Firestein GS, McInnes IB (2017) Immunopathogenesis of rheumatoid arthritis. Immunity 46:183–196CrossRefPubMed
Zurück zum Zitat Furst DE, Emery P (2014) Rheumatoid arthritis pathophysiology: update on emerging cytokine and cytokine-associated cell targets. Rheumatology 53:1560–1569CrossRefPubMedPubMedCentral Furst DE, Emery P (2014) Rheumatoid arthritis pathophysiology: update on emerging cytokine and cytokine-associated cell targets. Rheumatology 53:1560–1569CrossRefPubMedPubMedCentral
Zurück zum Zitat Harrington LE, Hatton RD, Mangan PR et al (2005) Interleukin 17–producing CD4 + effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132CrossRefPubMed Harrington LE, Hatton RD, Mangan PR et al (2005) Interleukin 17–producing CD4 + effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132CrossRefPubMed
Zurück zum Zitat Ichiyama K, Yoshida H, Wakabayashi Y et al (2008) Foxp3 inhibits RORγt-mediated IL-17A mRNA transcription through direct interaction with RORγt. J Biol Chem 283:17003–17008CrossRefPubMed Ichiyama K, Yoshida H, Wakabayashi Y et al (2008) Foxp3 inhibits RORγt-mediated IL-17A mRNA transcription through direct interaction with RORγt. J Biol Chem 283:17003–17008CrossRefPubMed
Zurück zum Zitat Ivanov II, Zhou L, Littman DR (2007) Transcriptional regulation of Th17 cell differentiation. Paper presented at the Seminars in immunology Ivanov II, Zhou L, Littman DR (2007) Transcriptional regulation of Th17 cell differentiation. Paper presented at the Seminars in immunology
Zurück zum Zitat Lee S-H, Han C-D, Yang I-H, Ha C-W (2011) Prescription pattern of NSAIDs and the prevalence of NSAID-induced gastrointestinal risk factors of orthopaedic patients in clinical practice in Korea. J Korean Med Sci 26:561–567CrossRefPubMedPubMedCentral Lee S-H, Han C-D, Yang I-H, Ha C-W (2011) Prescription pattern of NSAIDs and the prevalence of NSAID-induced gastrointestinal risk factors of orthopaedic patients in clinical practice in Korea. J Korean Med Sci 26:561–567CrossRefPubMedPubMedCentral
Zurück zum Zitat Metawi SA, Abbas D, Kamal MM, Ibrahim MK (2011) Serum and synovial fluid levels of interleukin-17 in correlation with disease activity in patients with RA. J Clin Rheumatol 30:1201CrossRef Metawi SA, Abbas D, Kamal MM, Ibrahim MK (2011) Serum and synovial fluid levels of interleukin-17 in correlation with disease activity in patients with RA. J Clin Rheumatol 30:1201CrossRef
Zurück zum Zitat Miossec P, Korn T, Kuchroo VK (2009) Interleukin-17 and type 17 helper T cells. N Engl J Med 361:888–898CrossRefPubMed Miossec P, Korn T, Kuchroo VK (2009) Interleukin-17 and type 17 helper T cells. N Engl J Med 361:888–898CrossRefPubMed
Zurück zum Zitat Mirshafiey A, Khorramizadeh MR, Saadatm F, Rehm BH (2004) Chemopreventive effect of M2000, a new anti-inflammatory agent. Med Sci Monit 10:PI105–PI109PubMed Mirshafiey A, Khorramizadeh MR, Saadatm F, Rehm BH (2004) Chemopreventive effect of M2000, a new anti-inflammatory agent. Med Sci Monit 10:PI105–PI109PubMed
Zurück zum Zitat Mirshafiey A, Cuzzocrea S, Rehm B, Matsuo H (2005a) M2000: a revolution in pharmacology. Med Sci Monit 11:PI53–PI63PubMed Mirshafiey A, Cuzzocrea S, Rehm B, Matsuo H (2005a) M2000: a revolution in pharmacology. Med Sci Monit 11:PI53–PI63PubMed
Zurück zum Zitat Mirshafiey A, Cuzzocrea S, Rehm B et al (2005b) Treatment of experimental arthritis with M2000, a novel designed non-steroidal anti-inflammatory drug. Scand J Immunol 61:435–441CrossRefPubMed Mirshafiey A, Cuzzocrea S, Rehm B et al (2005b) Treatment of experimental arthritis with M2000, a novel designed non-steroidal anti-inflammatory drug. Scand J Immunol 61:435–441CrossRefPubMed
Zurück zum Zitat Mirshafiey A, Matsuo H, Nakane S et al (2005c) Novel immunosuppressive therapy by M2000 in experimental multiple sclerosis. Immunopharm Immunot 27:255–265CrossRef Mirshafiey A, Matsuo H, Nakane S et al (2005c) Novel immunosuppressive therapy by M2000 in experimental multiple sclerosis. Immunopharm Immunot 27:255–265CrossRef
Zurück zum Zitat Mirshafiey A, Rehm B, Abhari RS et al (2007a) Production of M2000 (β-d-mannuronic acid) and its therapeutic effect on experimental nephritis. Environ Toxicol Pharmacol 24:60–66CrossRefPubMed Mirshafiey A, Rehm B, Abhari RS et al (2007a) Production of M2000 (β-d-mannuronic acid) and its therapeutic effect on experimental nephritis. Environ Toxicol Pharmacol 24:60–66CrossRefPubMed
Zurück zum Zitat Mirshafiey A, Rehm B, Sotoude M et al (2007b) Therapeutic approach by a novel designed anti-inflammatory drug, M2000, in experimental immune complex glomerulonephritis. Immunopharmacol Immunotoxicol 29:49–61CrossRefPubMed Mirshafiey A, Rehm B, Sotoude M et al (2007b) Therapeutic approach by a novel designed anti-inflammatory drug, M2000, in experimental immune complex glomerulonephritis. Immunopharmacol Immunotoxicol 29:49–61CrossRefPubMed
Zurück zum Zitat Movahedi M, Beauchamp ME, Abrahamowicz M et al (2016) Risk of incident diabetes mellitus associated with the dosage and duration of oral glucocorticoid therapy in patients with rheumatoid arthritis. Arthr Rheumatol 68:1089–1098CrossRef Movahedi M, Beauchamp ME, Abrahamowicz M et al (2016) Risk of incident diabetes mellitus associated with the dosage and duration of oral glucocorticoid therapy in patients with rheumatoid arthritis. Arthr Rheumatol 68:1089–1098CrossRef
Zurück zum Zitat Pène J, Chevalier S, Preisser L et al (2008) Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J Immunol 180:7423–7430CrossRefPubMed Pène J, Chevalier S, Preisser L et al (2008) Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J Immunol 180:7423–7430CrossRefPubMed
Zurück zum Zitat Prevoo M, Van’T Hof MA, Kuper H et al (1995) Modified disease activity scores that include twenty-eight-joint counts development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthr Rheumatol 38:44–48CrossRef Prevoo M, Van’T Hof MA, Kuper H et al (1995) Modified disease activity scores that include twenty-eight-joint counts development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthr Rheumatol 38:44–48CrossRef
Zurück zum Zitat Radner H, Aletaha D (2015) Anti-TNF in rheumatoid arthritis: an overview. Wien Med Wochenschr Suppl 165:3–9CrossRef Radner H, Aletaha D (2015) Anti-TNF in rheumatoid arthritis: an overview. Wien Med Wochenschr Suppl 165:3–9CrossRef
Zurück zum Zitat Shen H, Goodall JC, Hill Gaston J (2009) Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthr Rheumatol 60:1647–1656CrossRef Shen H, Goodall JC, Hill Gaston J (2009) Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthr Rheumatol 60:1647–1656CrossRef
Zurück zum Zitat Singh JA, Furst DE, Bharat A et al (2012) 2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthr Care Res 64:625–639CrossRef Singh JA, Furst DE, Bharat A et al (2012) 2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthr Care Res 64:625–639CrossRef
Zurück zum Zitat Van Den Berg WB, Miossec P (2009) IL-17 as a future therapeutic target for rheumatoid arthritis. Nat Rev Rheumatol 5:549–553CrossRefPubMed Van Den Berg WB, Miossec P (2009) IL-17 as a future therapeutic target for rheumatoid arthritis. Nat Rev Rheumatol 5:549–553CrossRefPubMed
Zurück zum Zitat van Hamburg JP, Asmawidjaja P, Davelaar N et al (2011) Th17 cells, but not Th1 cells, from patients with early rheumatoid arthritis are potent inducers of matrix metalloproteinases and proinflammatory cytokines upon synovial fibroblast interaction, including autocrine interleukin-17A production. Arthr Rheumatol 63:73–83CrossRef van Hamburg JP, Asmawidjaja P, Davelaar N et al (2011) Th17 cells, but not Th1 cells, from patients with early rheumatoid arthritis are potent inducers of matrix metalloproteinases and proinflammatory cytokines upon synovial fibroblast interaction, including autocrine interleukin-17A production. Arthr Rheumatol 63:73–83CrossRef
Zurück zum Zitat Youssouf L, Lallemand L, Giraud P et al (2017) Ultrasound-assisted extraction and structural characterization by NMR of alginates and carrageenans from seaweeds. Carbohydr Polym 166:55–63CrossRefPubMed Youssouf L, Lallemand L, Giraud P et al (2017) Ultrasound-assisted extraction and structural characterization by NMR of alginates and carrageenans from seaweeds. Carbohydr Polym 166:55–63CrossRefPubMed
Metadaten
Titel
Targeting of circulating Th17 cells by β-D-mannuronic acid (M2000) as a novel medication in patients with rheumatoid arthritis
verfasst von
Hossein Ahmadi
Mahdi Mahmoudi
Farhad Gharibdoost
Mahdi Vojdanian
Ahmad reza Jamshidi
Mohammad javad Fattahi
Zahra Aghazadeh
Anis Barati
Abbas Mirshafiey
Publikationsdatum
23.10.2017
Verlag
Springer International Publishing
Erschienen in
Inflammopharmacology / Ausgabe 1/2018
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-017-0410-8

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