Systemic administration of interleukin-4 expressing plasmid DNA delays the development of glomerulonephritis and prolongs survival in lupus-prone female NZB x NZW F1 mice
Systemic administration of interleukin-4 expressing plasmid DNA delays the development of glomerulonephritis and prolongs survival in lupus-prone female NZB x NZW F1 mice
复制标题
DOI：
10.1093/ndt/gfm465
复制
发表时间：
2007-11-01
影响因子：
6.1
通讯作者：
Maeda, Ken
中科院分区：
文献类型：
--
作者：
Hayashi, Toshiharu;Hasegawa, Keiko;Maeda, Ken
背景辅助性T细胞（Th）1/Th 2平衡决定了某些自身免疫性疾病的发生方向。Th 1细胞因子，特别是干扰素（IFN）-已被证明在狼疮的发病机制中的重要性。本研究检测了白细胞介素（IL）-4（Th 2细胞因子）表达质粒DNA（IL-4pDNA）对狼疮易感雌性NZB NZW（B/W）F-1小鼠肾小球肾炎发展和存活的影响。B/WF 1小鼠分别于4周龄、6周龄及8 ~ 32周龄每隔4周龄腹腔注射IL-4 pDNA（100 g/只）、质粒（100 g/只）或生理盐水。与生理盐水和质粒组（对照）相比，IL-4pDNA治疗显著延迟肾小球肾炎的发展，IgG 2a和C3的沉积导致尿蛋白排泄，并延长生存期。临床改善与IgG抗dsDNA自身抗体的产生减少有关。此外，与其他两种对照相比，IL-4pDNA处理减少了脾细胞IFN-γ的产生，并增加了IL-4的产生。目前的研究表明，全身IL-4pDNA管理可能会延迟狼疮发作的抑制IFN-γ的生产，由于从Th 1型向Th 2型反应的转变。
Background. T helper (Th)1/Th2 balance determines the direction of some kinds of autoimmune diseases. Th1 cytokines, especially interferon (IFN)- has been proven important in the pathogenesis in lupus. The present study examined the effects of administration of interleukin (IL)-4 (Th2 cytokine) expressing plasmid DNA (IL-4pDNA) on the development of glomerulonephritis and survival in lupus-prone female NZB NZW (B/W)F-1 mice.Methods. B/WF1 mice were administrated intraperitoneally either with IL-4pDNA (100g/mouse), plasmid (100g/mouse) or saline at 4 and 6 weeks of age and at 4 week intervals from 8 to 32 weeks of age.Results. Compared to the saline and plasmid groups (controls), the IL-4pDNA-treatment drastically delayed the development of glomerulonephritis with deposits of IgG2a and C3 leading to excretion of urine protein, and prolonged survival. Clinical improvement was associated with the reduction in productions of IgG anti-dsDNA autoantibody. Also, compared to the other two controls the IL-4pDNA-treatment reduced production of IFN- and increased IL-4 production from splenic cells.Conclusions. The present study suggests that systemic IL-4pDNA administration may delay lupus onset by suppressed IFN- production due to shifting from Th1 to Th2 responses.