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

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. 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. 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-1β 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. 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.