Bakhtiari Tahereh, Azarian ShahinKhadem, Ghaderi Afshin, Ahmadzadeh Arman, Mirshafiey Abbas
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Department of Internal Medicine, Hematology and Medical Oncology Ward, Cancer Research Centre, Cancer Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Allergy Asthma Immunol. 2019 Nov 11;18(6):639-648. doi: 10.18502/ijaai.v18i6.2176.
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).
类风湿性关节炎（RA）作为一种长期的自身免疫性疾病，其特征为疼痛、肿胀和关节破坏。在一项针对RA患者的I/II期临床试验中，已报道了古洛糖醛酸（G2013）（专利号：DEU: 102016113017.6）的治疗效果。在本研究中，我们旨在评估G2013作为一种具有免疫抑制特性的新型非甾体抗炎药（NSAID）对RA患者血样中抗炎和促炎细胞因子及其转录因子基因表达的影响。本研究对12例对传统治疗（改善病情抗风湿药（DMARDs）、NSAID和生物制剂）反应不佳的RA患者进行。G2013以每日两次、每次500 mg的剂量口服给药，持续12周。在使用G2013治疗患者前后，分离外周血单个核细胞（PBMCs），采用实时PCR方法评估白细胞介素10（IL10）、白细胞介素22（IL22）、干扰素γ（IFNγ）以及T辅助细胞谱系特异性转录因子叉头框P3（Fox-P3）、芳烃受体（AHR）和T细胞中表达的含T盒蛋白（T-bet）的基因表达水平。由于这些细胞因子在RA进展中起关键作用，且疾病状态预期会诱导IFNγ、AHR、IL22、T-bet表达，并降低IL10、Fox-P3表达。结果表明，与对照组相比，IFNγ、AHR水平显著降低，IL10、Fox-P3基因表达显著诱导。总之，本研究结果显示了G2013作为一种新型抗炎药的部分免疫机制，它可以减少促炎细胞因子及其转录因子。此外，它还增加了抗炎细胞因子及其转录因子（临床试验标识符：IRCT2016092813739N5）。
