Spermidine Inhibits Joints Inflammation and Macrophage Activation in Mice with Collagen-Induced Arthritis

Purpose: Spermidine (SPD) is a naturally occurring polyamine. In this study, we examined the role and possible mechanism of SPD in collagen-induced arthritis (CIA) mice. Materials and Methods: CIA mice were intraperitoneally injected with SPD (2 and 50 mg/kg), dexamethasone (0.5 mg/kg), or saline daily for 21 days. The severity of the disease and inflammatory responses in the serum and joint tissue were assessed through macroscopic, immunohistochemical, and histological analyses. Results: Macroscopic and histological results indicated that SPD protected against the development of CIA. SPD suppressed the levels of the pro-inflammatory cytokines IL-6 and IL-1 beta and increased the levels of the anti-inflammatory factor IL-10 in the serum. Immunohistochemical staining showed that 50 mg/kg SPD inhibited iNOS expression in synovial macrophages in the ankle joints of CIA mice. Conclusion: These results suggest that SPD may protect CIA mice by inhibiting the polarization of M1 macrophages in the synovial tissue, reducing pro-inflammatory cytokines, and promoting anti-inflammatory factor release.