Human, viral or mutant human IL-10 expressed after local adenovirus-mediated gene transfer are equally effective in ameliorating disease pathology in a rabbit knee model of antigen-induced arthritis.
Human, viral or mutant human IL-10 expressed after local adenovirus-mediated gene transfer are equally effective in ameliorating disease pathology in a rabbit knee model of antigen-induced arthritis.
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DOI：
10.1186/ar1960
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发表时间：
2006
影响因子：
4.9
通讯作者：
Robbins PD
中科院分区：
文献类型：
--
作者：
Keravala A;Lechman ER;Nash J;Mi Z;Robbins PD
IL-10是一种Th 2细胞因子，对抑制细胞介导的免疫同时促进体液应答很重要。人IL-10（hIL-10）具有抗炎、免疫抑制以及免疫刺激特性，而病毒IL-10（vIL-10），由Epstein巴尔病毒（EBV）编码的hIL-10的同源物，缺乏几种免疫刺激功能。hIL-10的免疫刺激特性归因于单个氨基酸，即位置87处的异亮氨酸，其在vIL-10中为丙氨酸。其中异亮氨酸已被取代的突变体hIL-10（mut.hIL-10）具有生物活性，仅具有免疫抑制功能，但不具有免疫刺激功能，使其成为炎性疾病的潜在上级治疗剂。为了比较mut.hIL-10与hIL-10和vIL-10在阻断类风湿性关节炎进展中的功效，我们使用复制缺陷型腺病毒载体将编码hIL-10、vIL-10或mut.hIL-10的基因关节内递送至兔的抗原诱导的关节炎（AIA）膝关节。hIL-10、vIL-10和mut.hIL-10的关节内表达导致治疗关节的病理学显著改善至相似水平。这些观察到的变化包括关节内白细胞增多和滑膜炎程度的显著降低，以及软骨基质代谢的正常化。我们的研究结果表明，hIL-10，vIL-10，和mut.hIL-10都是同样的治疗兔AIA模型治疗疾病的病理。
IL-10 is a Th2 cytokine important for inhibiting cell-mediated immunity while promoting humoral responses. Human IL-10 (hIL-10) has anti-inflammatory, immunosuppressive as well as immunostimulatory characteristics, whereas viral IL-10 (vIL-10), a homologue of hIL-10 encoded by Epstein Barr virus (EBV), lacks several immunostimulatory functions. The immunostimulatory characteristic of hIL-10 has been attributed to a single amino acid, isoleucine at position 87, which in vIL-10 is alanine. A mutant hIL-10 in which isoleucine has been substituted (mut.hIL-10) is biologically active with only immunosuppressive, but not immunostimulatory, functions, making it a potentially superior therapeutic for inflammatory diseases. To compare the efficacy of mut.hIL-10 with hIL-10 and vIL-10 in blocking the progression of rheumatoid arthritis, we used replication defective adenoviral vectors to deliver intra-articularly the gene encoding hIL-10, vIL-10 or mut.hIL-10 to antigen-induced arthritic (AIA) knee joints in rabbits. Intra-articular expression of hIL-10, vIL-10, and mut.hIL-10 resulted in significant improvement of the pathology in the treated joints to similar levels. These observed changes included a significant reduction in intra-articular leukocytosis and the degree of synovitis, as well as normalization of cartilage matrix metabolism. Our results suggest that hIL-10, vIL-10, and mut.hIL-10 are all equally therapeutic in the rabbit AIA model for treating disease pathology.
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影响因子：
2.4
作者：
Drazan, KE;Wu, L;Shaked, A
通讯作者：
Shaked, A
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ
影响因子：
15.3
作者：
Ding, Y;Qin, L;Kotenko, S V;Pestka, S;Bromberg, J S
通讯作者：
Bromberg, J S
影响因子：
3.7
作者：
GRAHAM, FL;VANDEREB, AJ
通讯作者：
VANDEREB, AJ
影响因子：
27.4
作者：
DIGIOVINE, FS;NUKI, G;DUFF, GW
通讯作者：
DUFF, GW