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Conditioned Medium from Estradiol-Primed Macrophages Mitigates Adjuvant-Induced Arthritis in Rats
Farshad Yadollahi1, Seyyed Meysam Abtahi Froushani1, Rahim Hobenaghi2
1Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
Advanced Pharmaceutical Bulletin
|March 16, 2026
Summary
Estradiol-treated macrophages produced conditioned medium that effectively reduced rheumatoid arthritis severity in rats. This cell-free therapy shows promise for treating inflammatory conditions like RA.
Area of Science:
- Immunology
- Endocrinology
- Pharmacology
Background:
- Macrophages play a crucial role in inflammation resolution and tissue repair.
- Estradiol influences macrophages towards an anti-inflammatory phenotype.
- Rheumatoid arthritis (RA) is a chronic inflammatory disease requiring effective therapeutic strategies.
Purpose of the Study:
- To evaluate the therapeutic potential of conditioned medium from estradiol-treated macrophages.
- To assess the efficacy of this cell-free secretome in an experimental model of rheumatoid arthritis.
Main Methods:
- Rheumatoid arthritis was induced in Wistar rats using complete Freund's adjuvant.
- Animals were treated with conditioned medium from untreated or estradiol-treated macrophages, vehicle, or prednisolone.
- Arthritis severity, weight gain, and inflammatory markers were assessed.
Main Results:
- Conditioned medium from estradiol-treated macrophages increased anti-inflammatory mediators (e.g., IL-10) and regulatory gene expression.
- This treatment significantly reduced arthritis severity and improved weight gain in rats.
- Key inflammatory markers (CRP, MPO, NO, IL-1, TNF-α) and bone-destructive factors (RANKL, MMP-9) were downregulated.
Conclusions:
- Conditioned medium from estradiol-treated macrophages is enriched with anti-inflammatory and regulatory molecules.
- This cell-free secretome represents a promising immunotherapy for rheumatoid arthritis.
- Further research into this approach could lead to novel RA treatments.

