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Updated: Jun 14, 2025
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
Therapeutic Effects of IL-1RA, M2 Cells, and Their Synergistic Impact on a Mouse Model of Rheumatoid Arthritis
Mohammad Sadegh Hashemzadeh1, Hadi Esmaeili Gouvarchin Ghaleh2, Mozafar Mohammadi3
1Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Purpose:
Rheumatoid arthritis (RA) is a type of autoimmune disease that results in chronic inflammation of the joint synovial tissue, leading to joint damage and significant disability. Despite ongoing research, the exact cause of RA remains unclear, and current treatments have limitations. This study explores the potential of utilizing interleukin-1 receptor antagonist (IL-1RA) and anti-inflammatory macrophages polarized in the vicinity of the supernatant from allogeneic mesenchymal stem cells (MSCs) as a novel therapeutic approach for RA.
Methods:
An expression cassette containing the IL-1RA gene was constructed and expressed in E. coli BL21. The resulting protein was purified and stabilized for use in in vivo experiments. Bone marrow MSCs were isolated and used to produce anti-inflammatory M2 macrophages from the isolated peripheral blood monocytes. The macrophages were then used to treat mice with RA induced by collagen type II.
Results:
The combination of IL-1RA and M2 macrophages improved clinical and histopathological symptoms of the disease, reduced levels of inflammatory factors, and modulated the immune system in the treated mouse groups. The results showed that this combinatory therapy had a synergistic effect for RA treatment.
Conclusion:
The simultaneous use of IL-1RA and M2 cells could be a promising approach for the treatment of RA. This combinatory therapy has the potential to improve the disease and decrease the severity of inflammation in patients with RA.
Insights
This study combined interleukin-1 receptor antagonist (IL-1RA) with anti-inflammatory M2 macrophages for rheumatoid arthritis (RA) treatment. The combination therapy showed synergistic effects, improving RA symptoms and reducing inflammation in mice.
Area of Science:
- Immunology
- Regenerative Medicine
- Pharmacology
Background:
- Rheumatoid arthritis (RA) is an autoimmune disease causing chronic joint inflammation, leading to damage and disability.
- Current RA treatments have limitations, and the exact cause remains unclear.
- Novel therapeutic strategies are needed to effectively manage RA.
Purpose of the Study:
- To explore the therapeutic potential of combining interleukin-1 receptor antagonist (IL-1RA) with anti-inflammatory M2 macrophages for rheumatoid arthritis (RA).
- To investigate a novel approach using IL-1RA and M2 macrophages derived from allogeneic mesenchymal stem cells (MSCs) for RA treatment.
Main Methods:
- Constructed and expressed the IL-1RA gene in E. coli, followed by protein purification.
- Isolated bone marrow MSCs to generate anti-inflammatory M2 macrophages from peripheral blood monocytes.
- Administered a combination therapy of IL-1RA and M2 macrophages to mice with collagen type II-induced RA.
Main Results:
- The combined IL-1RA and M2 macrophage therapy significantly improved clinical and histopathological symptoms of RA in mice.
- This combinatory approach reduced inflammatory factors and modulated the immune system effectively.
- Synergistic therapeutic effects were observed for RA treatment.
Conclusions:
- Simultaneous administration of IL-1RA and M2 macrophages presents a promising therapeutic strategy for RA.
- This combinatory therapy has the potential to enhance disease management and decrease inflammation severity in RA patients.
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