Direct adenovirus-mediated gene transfer of interleukin 1 and tumor necrosis factor α soluble receptors to rabbit knees with experimental arthritis has local and distal anti-arthritic effects
Direct adenovirus-mediated gene transfer of interleukin 1 and tumor necrosis factor α soluble receptors to rabbit knees with experimental arthritis has local and distal anti-arthritic effects
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DOI：
10.1073/pnas.95.8.4613
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发表时间：
1998-04-14
影响因子：
11.1
通讯作者：
Robbins, PD
中科院分区：
文献类型：
--
作者：
Ghivizzani, SC;Lechman, ER;Robbins, PD
使用腺病毒载体将编码可溶性白细胞介素1（IL-1）-I型受体-IgG融合蛋白和/或可溶性I型肿瘤坏死因子α（TNF α）受体-IgG融合蛋白的基因直接递送至患有抗原诱导性关节炎的兔膝关节。当单独测试时，接受可溶性IL-1受体的膝关节显著减少了软骨基质降解和白色血细胞浸润到关节间隙中。可溶性TNF α受体的递送不太有效，对白色血细胞浸润仅具有中等影响，对软骨破坏没有影响。当两种可溶性受体一起使用时，对白色血细胞浸润和软骨破坏有更大的抑制作用，滑膜炎显著减少。有趣的是，在仅接受标记基因的对侧对照膝关节中也观察到抗关节炎作用，这表明在一个关节中持续局部抑制疾病活性可赋予其他关节抗关节炎作用。这些结果表明，局部关节内基因转移可用于治疗系统性多关节炎。
Adenoviral vectors were used to deliver genes encoding a soluble interleukin 1 (IL-1)-type I receptor-IgG fusion protein and/or a soluble type I tumor necrosis factor alpha (TNF alpha) receptor-IgG fusion protein directly to the knees of rabbits with antigen-induced arthritis. When tested individually, knees receiving the soluble IL-1 receptor had significantly reduced cartilage matrix degradation and white blood cell infiltration into the joint space. Delivery of the soluble TNF alpha receptor was less effective, having only a moderate effect on white blood cell infiltration and no effect on cartilage breakdown. When both soluble receptors were used together, there was a greater inhibition of white blood cell infiltration and cartilage breakdown with a considerable reduction of synovitis. Interestingly, anti-arthritic effects were also seen in contralateral control knees receiving only a marker gene, suggesting that sustained local inhibition of disease activity in one joint mag confer an anti-arthritic effect on other joints. These results suggest that local intra-articular gene transfer could be used to treat systemic polyarticular arthritides.