Amelioration of established collagen induced arthritis by systemic IL-10 gene delivery
Amelioration of established collagen induced arthritis by systemic IL-10 gene delivery
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DOI：
10.1038/sj.gt.3301165
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发表时间：
2000-06-01
期刊：
影响因子：
5.1
通讯作者：
Woo, P
中科院分区：
文献类型：
--
作者：
Fellowes, R;Etheridge, CJ;Woo, P
使用含有新型细胞转染素 ACHx 的新型阳离子脂质体配方，将抗炎细胞因子基因 IL-10 递送至患有胶原诱导性关节炎的小鼠。在关节炎发作后2至4天，单次腹膜内注射与脂质体复合的人IL-10表达质粒足以使关节炎得到显着且持久的改善30天。初步实验表明，治疗效果呈IL-10剂量依赖性。注射后，人类 IL-10 DNA 分布广泛，包括发炎的爪子。注射后 24 小时，还在爪子中检测到人 IL-10 mRNA。 IL-10 蛋白低于爪子和血清中的缺陷水平，但在注射后长达 10 天的时间里在某些组织中出现缺陷。转染的靶细胞被证明是巨噬细胞。这些结果表明，质粒 DNA 与阳离子脂质体复合的全身治疗值得进一步开发，作为关节炎抗炎治疗的替代方法。
A novel formulation of cationic liposomes containing the novel cytofectin ACHx was used for delivery of an antiinflammatory cytokine gene, IL-10, to mice with established collagen induced arthritis. A single intraperitoneal injection of human IL-10 expression plasmid complexed with liposomes 2 to 4 days after the onset of arthritis was sufficient to give significant and prolonged amelioration of arthritis for 30 days. Preliminary experiments suggested that the therapeutic effect was IL-10 dose-dependent. The distribution of the human IL-10 DNA after injection was widespread, including the inflamed paws. Human IL-10 mRNA was also detected in the paws 24 h after injection. IL-10 protein was below the level of defection in paws and serum but was defected in some tissues up to 10 days after injection. The target cell of transfection was demonstrated to be the macrophage. These results suggest that systemic therapy with plasmid DNA complexed with cationic liposomes merits further development as an alternative method for antiinflammatory treatment of arthritis.