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

被引:30
作者
Kageyama, Y [1 ]
Koide, Y [1 ]
Uchijima, M [1 ]
Nagata, T [1 ]
Yoshida, A [1 ]
Taiki, A [1 ]
Miura, T [1 ]
Nagafusa, T [1 ]
Nagano, A [1 ]
机构
[1] Hamamatsu Univ Sch Med, Dept Orthopaed Surg, Hamamatsu, Shizuoka 43131, Japan
来源
ARTHRITIS AND RHEUMATISM | 2004年 / 50卷 / 03期
关键词
D O I
10.1002/art.20107
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
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/I 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.
引用
收藏
页码:968 / 975
页数:8
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