Case Control Study
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World J Clin Cases. Apr 6, 2021; 9(10): 2181-2191
Published online Apr 6, 2021. doi: 10.12998/wjcc.v9.i10.2181
Iguratimod promotes transformation of mononuclear macrophages in elderly patients with rheumatoid arthritis by nuclear factor-κB pathway
Sha Liu, Li-Ping Song, Rong-Bin Li, Le-Heng Feng, Hui Zhu
Sha Liu, Li-Ping Song, Rong-Bin Li, Le-Heng Feng, Hui Zhu, Department of Rheumatism, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital of Southern Medical University, Qiqihar 161005, Heilongjiang Province, China
Author contributions: All authors participated in the writing and final approval of the manuscript; Liu S, Zhu H, Song LP, and Li RB contributed to the conception and design of the study; Zhu H, Song LP, Li RB, and Feng LH performed the data collection and summarization; Liu S, Zhu H, Song LP, and Li RB performed the data analysis and interpretation.
Institutional review board statement: The study was reviewed and approved by the Medical Ethics Committee of Qiqihar First Hospital.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: The authors give informed consent to data sharing.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hui Zhu, MPhil, Associate Chief Physician, Department of Rheumatism, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital of Southern Medical University, No. 30 Gongyuan Road, Longsha District, Qiqihar 161005, Heilongjiang Province, China. zhuhui0223@163.com
Received: December 11, 2020
Peer-review started: December 11, 2020
First decision: December 30, 2020
Revised: January 13, 2021
Accepted: February 11, 2021
Article in press: February 11, 2021
Published online: April 6, 2021
Processing time: 108 Days and 23 Hours
Abstract
BACKGROUND

The 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.

AIM

To investigate the effects of Iguratimod on the polarity of mononuclear macrophages in elderly patients with RA.

METHODS

Elderly 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.

RESULTS

Disease 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).

CONCLUSION

Iguratimod 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.

Keywords: Rheumatoid arthritis; Iguratimod; Macrophage; Polarity; Nuclear factor-κB

Core Tip: Elderly patients with rheumatoid arthritis (RA) with effusion in the joint cavity were treated by Iguratimod. Compared with before treatment, Disease Activity Score 28 score and Health Assessment Questionnaire score were decreased, the percentage of CD86 and CD64 decreased, the percentage of CD163 and CD 206 increased, interleukin (IL)-6 and IL-1β was reduced, while transforming growth factor-β and IL-4 was increased. Inhibitor of nuclear factor-κB (NF-κB) was expressed more, but phosphorylated inhibitor of NF-κB was expressed less, which suggested that Iguratimod can promote the transformation of monocyte macrophages from M1 type to M2 type in elderly patients with RA by inhibiting the NF-κB pathway, thus improving the symptoms of RA.