Systemic delivery of C II TA siRNA reduces disease severity in collagen-induced arthritis

Objective: To examine the therapeutic effect of C II TA inhibition in collagen-induced arthritis (CIA), using a delivery system tailored to target C II TA gene by small interfering RNA (siRNA). Methods: Mice with collagen-induced arthritis were injected intravenously with C II TA siRNA. The clinical score was monitored for up to 4 weeks after treatment. The severity of inflammation of mouse joint was evaluated by histological examination. Real-time PCR was used to determine the cytokine mRNA expression. Cytokine production was measured by ELISA from serum. T cell proliferation was examined by MTT method. Results: IFN-γ and IL-17 were elevated in CIA mice, but were inhibited significantly by C II TA siRNA either prevention or intervention of autoimmune arthritis. Collagen specific T cell proliferation was significantly suppressed. Increased level of IL-4 by T cells was observed in C II TA siRNA treated group compared with that of control group. Conclusion: Our findings indicate that systemic RNAi-mediated C II TA gene silencing is effective in the treatment of CIA and regulateds the balance of Th1/Th2 differentiation.