AB0523 Metformin combined with conventional therapy increases absolute number of regulatory t cells in patients with systemic lupus erythematosus
Authors: M. Hao, Z. Liang, X. Jing, X.Q. Liu, C. gao, X. li, J. chen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is multisystem and multiorgan autoimmune diseases and the main treatment is hormone combined with immunosuppressant and biological agents. Since the conventional treatment regimens have not achieved expected effects, it is of great practical value to search for good efficacy, lower side-effects, and low-cost drugs. Recently, we have found that the absolute number of CD4<sup>+</sup>CD25<sup>+</sup>FOXP3<sup>+</sup> regulatory T (CD4<sup>+</sup> Treg) cells reduced in SLE. Metformin, a basic hypoglycemic drug, has been shown to increase the number of Treg cells and decrease the number of Th17 cells.<sup>[1,2,3]</sup> <h3>Objectives</h3> To observe the clinical efficacy of metformin on the treatment of SLE and levels of CD4 +Treg and Th17 cells. <h3>Methods</h3> Twenty-three patients with SLE were enrolled in this study. They fulfilled the <sup>ACR 1997</sup> standard, their average age was 32.22±8.18 years, and duration was 51.41±15.52 months. These patients were administered metformin (250 mg Bid) combined with conventional therapy for 6 weeks. At week 0 and week 6, the absolute numbers of Th17 cells and Treg, the symptoms, and laboratory indicators were collected. <h3>Results</h3> After metformin treatment combined with conventional therapy, average absolute number of Treg cells in 23 patients increased significantly from20.2 (20.28) (week 0) to 25.76 (25.1) (week 6) (p=0.073) while that of Th17 cells increased slightly from5.29 (6.43) (week 0) to 5.57 (6.05) (week 6) (p=0.956), which led to reduce average ratio of Th17/Treg from 0.25 (0.31) (0 week) to 0.19 (0.23) (6 weeks) (p=0.147). The treatment attenuated the symptoms of the patients and meantime, the dose of prednisone was decreased. At week 6, metformin combined with interleukin-2, the dosage of prednisone in SLE patients were decreased from 23.70±19.41 mg/d(0 week) to 20.44±17.03 mg/d(6 weeks) (p=0.548). <h3>Conclusions</h3> Our findings suggest metformin can effectively up-regulate Treg cells as well as increase Th17 to a certain extent, which restores the balance of Th17/Treg cells in SLE, metformin combined with conventional therapy can reduce the dosage of glucocorticoid, but the long-term effect needs further investigation. <h3>References</h3> [1] Michalek RD, Gerriets VA, Jacobs SR, et al. Cutting edge: Distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets[J]. J Immuno12011;186(6):3299–3303. doi:10.4049/jimmunol.1003613 [Epub 2011 Feb 11]. [2] Kang KY, Kim YK, Yi H, et al. Metformin downregulates Th17 cells differentiation and attenuates murine autoimmune arthritis [J]. Int Immunopharmacol2013;16(1):85–92. doi:10.1016/j.intimp.2013.03.020 [3] Sun Y, Tian T,Gao J, et al. Metformin ameliorates the development of experimental autoimmune encephalomyelitis by regulating T helper 17 and regulatory T cells in mice [J]. J Neuroimmunol2016;292:58–67. doi:10.1016/j.jneuroim.2016.01.014 <h3>Disclosure of Interest</h3> None declared