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OBJECTIVE: Viral interleukin 10 (vIL-10) has a variety of immunomodulatory properties. We examined the applicability of vIL-10 gene transfer to the treatment of mice with arthrogen-collagen-induced arthritis (CIA), which is induced by anti-type II collagen antibodies. METHODS: One day after anti-type II collagen antibodies were injected into mice, 400 microg of plasmid DNA expressing vIL-10 (pCAGGS-vIL-10) was injected into the bilateral tibialis anterior muscles followed by in vivo electroporation consisting of four 50-ms electric pulses of 100 V (pCAGGS-vIL-10 mice). pCAGGS (400 microg) was similarly injected into control mice (pCAGGS mice). RESULTS: We observed high serum vIL-10 levels in the pCAGGS-vIL-10 mice, but no vIL-10 was detected in the serum of the pCAGGS mice. Using quantitative real-time polymerase chain reaction, we observed that the ratios of IL-6, tumor necrosis factor-a, and IL-1beta transcripts to those of G6PDH in the joints were significantly lower in the pCAGGS-vIL-10 mice than in the pCAGGS mice (p < 0.05). The pCAGGS-vIL-10 mice showed significant therapeutic effects: the severity of the macroscopic arthritis was significantly suppressed from Days 5 to 21 (p < 0.0001), and the histologically observable development of arthritis was also suppressed in these mice on Day 21 (p < 0.0001). CONCLUSION: These results demonstrated that pCAGGS-vIL-10 gene transfer by in vivo electroporation suppressed arthrogen-CIA.