Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 18 6 2019 11 11 639 648 EN Tahereh Bakhtiari Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran ShahinKhadem Azarian Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran Afshin Ghaderi Department of Internal Medicine, Hematology and Medical Oncology Ward, Cancer Research Centre, Cancer Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Arman Ahmadzadeh Department of Rheumatology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Abbas Mirshafiey Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran AND Research Center for Immunodeficiencies, Children's Medical Centre, Tehran University of Medical Sciences, Tehran, Iran 2019 05 26 2019 07 10 Rheumatoid arthritis (RA) as a long-term autoimmune disease is characterized by pain, swelling and joints destruction. The therapeutic efficacy of Guluronic acid (G2013) (patented, DEU: 102016113017.6) was reported in phase I/II clinical trial in RA patients. In this study, we aimed to evaluate the effect of G2013 as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive property on genes expression of anti-inflammatory and pro-inflammatory cytokines and their transcription factors in the blood sample of RA patients. This study was performed on 12 patients with RA who had an inadequate response to conventional treatments which were disease-modifying anti-rheumatic drugs (DMARDs), NSAID, and biologics. G2013 was administered orally at a dose of 500 mg twice daily for 12 weeks. Before and after the treatment of patients with drug G2013, the peripheral blood mononuclear cells (PBMCs) were isolated for evaluating the gene expression level of interleukin 10 (IL10), interleukin 22 (IL22), interferon γ (IFNγ), and transcription factors specific to the T helper cell lineages, forkhead box P3 (Fox-P3), Aryl hydrocarbon receptor (AHR) and T-box–containing protein expressed in T cells (T-bet) using the real-time PCR method. Since these cytokines have a key role in the progression of RA and disease condition expected induction of IFNγ, AHR, IL22, T-bet, and reduction of IL10, Fox-P3. Results indicated a significant reduction in the level of IFNγ, AHR and a significant induction in IL10, Fox-P3 gene expression in comparison with the control group. In conclusion; the results of this investigation showed a part of the immunological mechanism of G2013 as a novel anti-inflammatory that could reduce pro-inflammatory cytokine and their transcription factors. Furthermore, it increased the anti-inflammatory cytokine and its transcription factor (clinical trial identifier: IRCT2016092813739N5). https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2418