Mohammad Javad Fattahi1, Hossein Ahmadi2, Fahimeh Jafarnezhad-Ansariha3, Seyed Shahabeddin Mortazavi-Jahromi4, Bernd H A Rehm5, Salvatore Cuzzocrea6, Hidenori Matsuo7, Abbas Mirshafiey8. 1. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. 2. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. 3. Department of Immunology, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. 4. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Department of Cellular and Molecular Biology, Kish International Campus, University of Tehran, Kish, Iran. 5. Centre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, QLD, Australia. 6. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy. 7. Department of Clinical Research, Nagasaki Kawatana Medical Center, Nagasaki, Japan; Department of Neurology, Nagasaki Kawatana Medical Center, Nagasaki, Japan. 8. Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: mirshafiey@tums.ac.ir.
Abstract
BACKGROUND: To explore the effects of β-d-mannuronic acid (M2000) on levels of Th17, regulatory T (Treg) cells and their related cytokines in patients with ankylosing spondylitis (AS). METHODS: 30 AS patients and 15 age and sex-matched healthy individuals were enrolled in this study. The frequencies of Th17 and Treg cells and serum levels of related cytokines were measured by flow cytometry analysis and ELISA respectively, before (baseline) and 3 months after M2000 therapy. RESULTS: Significantly higher baseline Th17 cells and serum IL-17, TNF-α and IL-6 were observed in AS patients than in normal controls, whereas baseline levels of Treg cells and serum IL-10 were not significantly different between AS patients and healthy controls. After M2000 therapy, frequencies of Th17 and serum levels of IL-17 and IL-6 significantly decreased in AS patients. The frequencies of Treg cells and serum level of IL-10 were not significantly changed, in comparison to before therapy. Moreover, the correlation analysis showed that frequencies of Th17 and levels of IL-17, TNF-α and IL-6 were positively correlated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) scores, whereas Treg cells were revealed to be negatively correlated with BASDAI and BASFI scores. CONCLUSIONS: It can be concluded that the oral administration of M2000 as a novel NSAID with the immunosuppressive property that down-regulates Th17 and Th17-related cytokines and facilitates the correction of the Th17/Treg imbalance can be effective in the process of AS treatment.
BACKGROUND: To explore the effects of β-d-mannuronic acid (M2000) on levels of Th17, regulatory T (Treg) cells and their related cytokines in patients with ankylosing spondylitis (AS). METHODS: 30 AS patients and 15 age and sex-matched healthy individuals were enrolled in this study. The frequencies of Th17 and Treg cells and serum levels of related cytokines were measured by flow cytometry analysis and ELISA respectively, before (baseline) and 3 months after M2000 therapy. RESULTS: Significantly higher baseline Th17 cells and serum IL-17, TNF-α and IL-6 were observed in AS patients than in normal controls, whereas baseline levels of Treg cells and serum IL-10 were not significantly different between AS patients and healthy controls. After M2000 therapy, frequencies of Th17 and serum levels of IL-17 and IL-6 significantly decreased in AS patients. The frequencies of Treg cells and serum level of IL-10 were not significantly changed, in comparison to before therapy. Moreover, the correlation analysis showed that frequencies of Th17 and levels of IL-17, TNF-α and IL-6 were positively correlated with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) scores, whereas Treg cells were revealed to be negatively correlated with BASDAI and BASFI scores. CONCLUSIONS: It can be concluded that the oral administration of M2000 as a novel NSAID with the immunosuppressive property that down-regulates Th17 and Th17-related cytokines and facilitates the correction of the Th17/Treg imbalance can be effective in the process of AS treatment.