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Effects of Viral Interleukin 10 Introduced by in vivo Electroporation on Arthrogen-Induced Arthritis in Mice

TAKESHI KURODA, HIROKI MARUYAMA, MASAAKI SHIMOTORI, NOBORU HIGUCHI, SHIGEMI KAMEDA, HIDEAKI TAHARA, JUN-ICHI MIYAZAKI, and FUMITAKE GEJYO

ABSTRACT.

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 µg 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 µg) 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-1ß 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. (J Rheumatol 2006;33:455-62)

Key Indexing Terms:

ARTHROGEN-INDUCED ARTHRITIS
MOUSE
GENE THERAPY
ELECTROPORATION
VIRAL INTERLEUKIN 10


From the Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City; Department of Surgery, Institute of Medical Science, University of Tokyo, Tokyo; and Division of Stem Cell Regulation Research, Osaka University Medical School, Osaka, Japan.

T. Kuroda, MD, PhD, FJSIM, Assistant Professor; H. Maruyama, MD, PhD, Associate Professor; M. Shimotori, MD, Fellow; N. Higuchi, MD, PhD, Fellow; S. Kameda, MD, PhD, Fellow, Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences; H. Tahara, MD, PhD, Professor, Department of Surgery, Institute of Medical Science, University of Tokyo; J. Miyazaki, MD, PhD, Professor, Division of Stem Cell Regulation Research, G6, Osaka University Medical School; F. Gejyo, MD, PhD, Professor, Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences.

Address reprint requests to Dr. H. Maruyama, Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata City, 9 51-8510, Japan. E-mail:hirokim@med.niigata-u.ac.jp

Accepted for publication November 9, 2005.


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