IL-4 adenoviral gene therapy reduces inflammation, proinflammatory cytokines, vascularization, and bony destruction in rat adjuvant-induced arthritis
IL-4 adenoviral gene therapy reduces inflammation, proinflammatory cytokines, vascularization, and bony destruction in rat adjuvant-induced arthritis
复制标题
DOI：
10.4049/jimmunol.166.2.1214
复制
发表时间：
2001-01-15
影响因子：
4.4
通讯作者：
Kock, AE
中科院分区：
文献类型：
--
作者：
Woods, JM;Katschke, KJ;Kock, AE
IL-4 是一种对活化的巨噬细胞具有抗炎特性的细胞因子。类风湿性关节炎是一种自身免疫性炎症疾病，其特征是 IL-4 缺乏和滑膜巨噬细胞衍生介质丰富。在此，将单次注射产生腺病毒的大鼠IL-4 (AxCAIL-4)或没有插入基因的对照病毒的效果与将PBS注射到大鼠脚踝的效果进行比较。在关节炎发作前或炎症最严重时注射脚踝。预防性地，AxCAIL-4 减少佐剂诱导的关节炎 (AIA) 和/或 AIA/腺病毒诱导的踝关节炎症，降低关节指数评分、踝关节周长、爪体积、放射学评分、单核细胞趋化蛋白 1 的平均水平、炎症细胞的数量和滑膜血管的数量。与未插入基因的对照病毒和 PBS 组相比，AxCAIL-4 还减少了脚踝周长和爪子体积。关节炎发作后，与 PBS 处理的匀浆相比，AxCAIL-4 大鼠踝匀浆中 TNF-α、IL-1β、巨噬细胞炎症蛋白 2 和 RANTES 的平均水平降低。因此，通过以预防和/或治疗方式施用的基因疗法增加IL-4的表达可减少大鼠AIA中的关节炎症、滑膜细胞构成、促炎细胞因子水平、血管化和骨破坏，这表明在人类中进行类似治疗可能是有益的。
IL-4 is a cytokine with anti-inflammatory properties on activated macrophages. Rheumatoid arthritis, an autoimmune inflammatory disease, is characterized by a paucity of IL-4 and an abundance of synovial macrophage-derived mediators. Herein, the effect of a single injection of adenovirus-producing rat IL-4 (AxCAIL-4) or a control virus with no inserted gene was compared with the effect of PBS injection into rat ankles, Ankles were injected before arthritis onset or at maximal inflammation. Preventatively, AxCAIL-4 reduced adjuvant-induced arthritis (AIA)- and/or AIA/adenoviral-induced ankle inflammation, decreasing articular index scores, ankle circumferences, paw volumes, radiographic scores, mean levels of monocyte chemoattractant protein-1, the number of inflammatory cells, and the number of synovial blood vessels. Therapeutically, AxCAIL-4 also decreased ankle circumferences and paw volumes in comparison with a control virus with no inserted gene and PBS groups. After arthritis onset, mean levels of TNF-alpha, IL-1 beta, macrophage inflammatory protein-2, and RANTES were decreased in AxCAIL-4 rat ankle homogenates compared with PBS-treated homogenates. Thus, increased expression of IL-4 via gene therapy administered in a preventative and/or therapeutic manner reduced joint inflammation, synovial cellularity, levels of proinflammatory cytokines, vascularization, and bony destruction in rat AIA, suggesting that a similar treatment in humans may be beneficial.