Plasmid encoding interleukin-4 in the amelioration of murine collagen-induced arthritis

OBJECTIVE: To evaluate the therapeutic effect of the administration of plasmid encoding interleukin-4 (IL-4) via gene-gun delivery and via intradermal injection on collagen-induced arthritis (CIA). METHODS: IL-4 plasmid was administered by gene-gun delivery and intradermal injection to DBA/1 mice immunized with type II collagen (CII). The therapeutic effect on the development of CIA was evaluated clinically with a visual scoring method for arthritis and serologically by enzyme-linked immunosorbent assays and polymerase chain reaction. RESULTS: Treatment with IL-4-expressing plasmid significantly reduced the incidence and severity of CIA, including a reduction in the anti-CII antibody level. In particular, gene-gun delivery had a higher immunosuppressive effect on CIA compared with intradermal injection. As shown by in vitro stimulation assay, the spleen cells from mice immunized with CII and treated with IL-4 plasmid via gene gun exhibited higher Th2 cytokine responses compared with cells treated with control plasmid after in vitro stimulation with CII. CONCLUSION: The results of this study suggest that treatment with IL-4 plasmid may constitute a new clinical use of cytokine gene therapy for rheumatoid arthritis.