Iguratimod promotes transformation of mononuclear macrophages in elderly patients with rheumatoid arthritis by nuclear factor-κB pathway.

Abstract

BACKGROUNDThe role of macrophages in rheumatoid arthritis (RA) and its mechanism have attracted much attention in RA pathogenesis. Macrophages accumulate in the synoviums of RA, and the proportion of M1 type pro-inflammatory macrophages is higher than that of M2 type anti-inflammatory macrophages, leading to the secretion of inflammatory molecules and the aggravation of inflammatory reaction, which has made macrophages a potential target of RA drugs. Iguratimod is a kind of cyclo-oxygenase-2 inhibitor that affects macrophage polarity. It is speculated that its anti-inflammatory and anti-rheumatic effects may be related to the regulation of macrophage M1/M2 ratio.AIMTo investigate the effects of Iguratimod on the polarity of mononuclear macrophages in elderly patients with RA.METHODSElderly patients with RA and joint effusion were selected, including 10 men and 25 women, with an average age of 66.37 ± 4.42 years. Patients were treated with oral administration of 25 mg Iguratimod (Iremod, State Food and Drug Administration Approval No. H20110084) twice daily for 12 wk. Disease Activity Score 28 and Health Assessment Questionnaire score were collected according to the disease severity before and after treatment. Venous blood and joint effusion fluid were collected, mononuclear macrophages were extracted and expression of cell surface markers CD86, CD64, CD163, and CD206 was analyzed by flow cytometry. The concentration of inflammatory factors interleukin (IL)-6, IL-1β, transforming growth factor-β, and IL-4 in the joint effusion fluid was analyzed by enzyme-linked immunosorbent assay. Expression of mononuclear cells inhibitor of nuclear factor-κB (IκB) and phosphorylated IκB in peripheral blood was analyzed by western blotting. RESULTSDisease Activity Score 28 score and Health Assessment Questionnaire score of patients treated with Iguratimod decreased significantly. The percentage of cell surface markers CD86 and CD64 decreased significantly, and the percentage of CD163 and CD206 increased significantly (P < 0.05). The inflammatory factors IL-6 and IL-1β decreased significantly, and transforming growth factor-β and IL-4 increased significantly. Western blot analysis showed that mononuclear cell inhibitor of nuclear factor-κB in peripheral blood was significantly increased after treatment, and its phosphorylation level was significantly decreased (P < 0.05).CONCLUSIONIguratimod can promote the transformation of mononuclear macrophages from M1 to M2 in elderly patients with RA by inhibiting the nuclear factor-κB pathway, thus improving symptoms of RA.