Hematological Improvement of Patients with Active Rheumatoid Arthritis by β-D-Mannuronic Acid (M2000) as a Novel NSAID with Immunosuppressive Property

Iran J Allergy Asthma Immunol. 2017 Oct;16(5):433-442.

Abstract

The aim of this study was to investigate the effect of β-D-mannuronic acid (M2000) on hematological parameters in patients with active rheumatoid arthritis. This study was conducted on 25 patients with active rheumatoid arthritis (RA) (identifier: IRCT2014011213739N2). M2000 was administered orally for anemic and non-anemic RA patients at a dose of 500 mg twice daily for 12 weeks. The patients were permitted to continue the conventional treatments excluding NSAIDs. Blood samples were collected at baseline, 4 and 12 weeks after drug administration and were tested for hematological parameters. Moreover, serum levels of TNF-α and IL-6 were analysed before and after M2000 therapy compared to healthy controls using enzyme linked immunosorbent assay method. We found a significant increase in the count of red blood cells and also hemoglobin (Hb) concentration (0.9 g/dL) in anemic patients after 12 weeks of M2000 therapy (p<0.02 and p<0.01, respectively). Furthermore, our results showed an improvement in Hb level (0.45 g/dL) even in non-anemic patients who were treated by M2000 (p<0.04). The leukocytosis in RA patients, significantly decreased in both anemic and non-anemic patients after 12 weeks of M2000 therapy (p<0.02 and p<0.03, respectively). The percent of neutrophils significantly increased in anemic patients (p<0.01) while in non-anemic patients it significantly decreased after 12 weeks of M2000 therapy (p<0.01). The serum levels of IL-6 and TNF-α significantly decreased after 12 weeks of M2000 therapy (p<0.01 and p<0.04, respectively). M2000 improves hematological parameters in RA patients by its potent inhibitory effect on serum levels of TNF-α and IL-6.

Keywords: Anemia; Inflammation; Interleukin; M2000; Mannuronic acid; Rheumatoid arthritis; Therapy.

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Biomarkers
  • Cytokines / blood
  • Cytokines / metabolism
  • Erythrocyte Indices / drug effects
  • Female
  • Hexuronic Acids / pharmacology
  • Hexuronic Acids / therapeutic use*
  • Humans
  • Immunosuppressive Agents / immunology
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Inflammation Mediators / metabolism
  • Leukocyte Count
  • Male
  • Middle Aged
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Cytokines
  • Hexuronic Acids
  • Immunosuppressive Agents
  • Inflammation Mediators
  • mannuronic acid