Interleukin-13 gene therapy reduces inflammation, vascularization, and bony destruction in rat adjuvant-induced arthritis.
Interleukin-13 gene therapy reduces inflammation, vascularization, and bony destruction in rat adjuvant-induced arthritis.
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DOI：
10.1089/10430340252792512
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发表时间：
2002-02
影响因子：
4.2
通讯作者：
J. Woods;M. Amin;K. Katschke;M. Volin;J. Ruth;M. A. Connors;D. Woodruff;H. Kurata;K. Arai;G. Haines;Pawan Kumar;A. Koch
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文献类型：
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作者：
J. Woods;M. Amin;K. Katschke;M. Volin;J. Ruth;M. A. Connors;D. Woodruff;H. Kurata;K. Arai;G. Haines;Pawan Kumar;A. Koch
类风湿性关节炎（RA）是一种慢性自身免疫性炎症性疾病，其特征是滑膜血管翳形成、白细胞浸润和血管生成。腺病毒介导的白细胞介素-13（IL-13）的产生降低了体外RA滑膜组织移植模型中促炎介质的水平。为了在关节炎动物模型中评估这种方法，我们比较了关节内注射腺病毒产生大鼠IL-13（AxCArIL-13），对照病毒，以及大鼠踝关节接受磷酸盐缓冲盐水（PBS）在大鼠佐剂诱导的关节炎（AIA）中的作用。我们证明，IL-13水平通常是低的，在整个过程中的大鼠AIA的踝关节。我们表明，在关节炎发作前给予AxCArIL-13显著降低了踝关节周长、爪体积、骨破坏、多形核细胞（PMN）数量、血管数量和踝关节中单核细胞趋化蛋白（MCP）-1水平。当作为治疗给药至发炎的踝关节时，AxCArIL-13降低关节指数评分、爪体积、骨破坏、血管形成、肿瘤坏死因子-α（TNF-α）水平以及单核细胞、淋巴细胞和PMN的量。因此，增加IL-13水平显着改善大鼠AIA的过程中，这表明类似的策略治疗人类RA值得进一步研究。
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovial pannus formation, leukocyte infiltration, and angiogenesis. Adenoviral production of interleukin-13 (IL-13) reduces levels of proinflammatory mediators in an explant model of RA synovial tissue in vitro. To assess this approach in an animal model of arthritis, we compared intra-articular injections of an adenovirus producing rat IL-13 (AxCArIL-13), a control virus, and rat ankles receiving phosphate-buffered saline (PBS) in rat adjuvant-induced arthritis (AIA). We demonstrate that IL-13 levels are normally low in ankles throughout the course of rat AIA. We show that administration of AxCArIL-13 before arthritis onset significantly reduces ankle circumference, paw volume, bony destruction, the number of polymorphonuclear cells (PMNs), the quantity of blood vessels, and levels of monocyte chemoattractant protein (MCP)-1 in ankles. When administered as a treatment to inflamed ankles, AxCArIL-13 decreases articular index scores, paw volumes, bony destruction, vascularization, tumor necrosis factor-alpha (TNF-alpha) levels, and the quantity of monocytes, lymphocytes, and PMNs. Thus, increasing IL-13 levels significantly ameliorates the course of rat AIA, suggesting that similar strategies for the treatment of human RA are worthy of further study.