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Iguratimod promotes transformation of mononuclear macrophages in elderly patients with rheumatoid arthritis by
Sha Liu1, Li-Ping Song1, Rong-Bin Li1
1Department of Rheumatism, The First Hospital of Qiqihar, Affiliated Qiqihar Hospital of Southern Medical University, Qiqihar 161005, Heilongjiang Province, China.
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.
Insights
Iguratimod effectively shifts pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages in elderly rheumatoid arthritis patients. This macrophage polarization improves RA symptoms by reducing inflammation via the nuclear factor-kappa B pathway.
Area of Science:
- Immunology
- Rheumatology
- Pharmacology
Background:
- Macrophages play a key role in rheumatoid arthritis (RA) pathogenesis, with M1 pro-inflammatory macrophages dominating over M2 anti-inflammatory macrophages in RA synovium.
- This imbalance exacerbates inflammation and RA progression, making macrophages a therapeutic target.
- Iguratimod, a cyclooxygenase-2 inhibitor, influences macrophage polarity, suggesting a potential mechanism for its anti-rheumatic effects.
Purpose of the Study:
- To investigate the impact of Iguratimod on the polarization of mononuclear macrophages in elderly patients diagnosed with RA.
- To assess the therapeutic efficacy of Iguratimod in improving clinical symptoms and inflammatory markers associated with RA.
Main Methods:
- Elderly RA patients with joint effusion received oral Iguratimod (25 mg twice daily for 12 weeks).
- Disease activity and functional status were assessed using Disease Activity Score 28 and Health Assessment Questionnaire.
- Mononuclear macrophage surface markers (CD86, CD64, CD163, CD206), inflammatory cytokines (IL-6, IL-1β, TGF-β, IL-4), and NF-κB pathway components (IκB, p-IκB) were analyzed.
Main Results:
- Iguratimod treatment significantly reduced Disease Activity Score 28 and Health Assessment Questionnaire scores.
- Macrophage analysis revealed a significant decrease in M1 markers (CD86, CD64) and an increase in M2 markers (CD163, CD206).
- Levels of pro-inflammatory cytokines IL-6 and IL-1β decreased, while anti-inflammatory cytokines TGF-β and IL-4 increased, alongside increased IκB and decreased p-IκB in peripheral blood mononuclear cells.
Conclusions:
- Iguratimod promotes the M1 to M2 macrophage polarization in elderly RA patients.
- This shift in macrophage polarity, mediated by the inhibition of the nuclear factor-kappa B pathway, contributes to the improvement of RA symptoms.
- Iguratimod demonstrates therapeutic potential for managing rheumatoid arthritis by modulating macrophage function.
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