Involvement of IL-6, apart from its role in immunity, in mediating a chronic response during experimental arthritis
Involvement of IL-6, apart from its role in immunity, in mediating a chronic response during experimental arthritis
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DOI：
10.1016/s0002-9440(10)64846-8
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发表时间：
2000-12-01
影响因子：
6
通讯作者：
van den Berg, WB
中科院分区：
文献类型：
--
作者：
de Hooge, ASK;van de Loo, FAJ;van den Berg, WB
白细胞介素-6（IL-6）在关节炎期间大量产生，但其确切功能仍不清楚。在这项研究中，我们研究了IL-6，除了其在免疫中的作用，是否参与了实验性关节炎的局部炎症反应。首先比较IL-6缺陷型（IL-6（-/-））和野生型小鼠。在抗原诱导的关节炎模型中。IL-6缺乏导致轻微的、短暂的炎症，而野生型小鼠发展为慢性的、破坏性的滑膜炎。用正常抗原剂量的十分之一免疫的野生型小鼠尽管抗体水平低，但仍发展为慢性关节炎，不包括IL-6（-/-）小鼠中的体液免疫降低作为关键现象。此外，被动免疫复合物诱导的关节炎在野生型和IL-6（-/-）小鼠之间没有差异。另一种选择是降低IL-6（-/-）小鼠中Th 1细胞的水平，然而，将抗原特异性野生型淋巴结细胞转移到IL-6（-/-）小鼠中增强了急性关节炎症和增加了软骨损伤，但仍然不能维持慢性炎症，这表明IL-6活性的非免疫元件参与慢性化。与此一致，非免疫介导的酵母聚糖诱导的关节炎在第一周也发生了类似的发展，但只有野生型小鼠出现了慢性滑膜炎。这些结果表明IL-6在关节炎症传播中的重要作用，可能独立于其在免疫中的作用。
Interleukin-6 (IL-6) is highly produced during arthritis but its exact function is still unknown. In this study we examined if IL-6, apart from its role in immunity, was involved in the local inflammatory response in experimental arthritis. IL-6 deficient (IL-6(-/-)) and wild-type mice were first compared. in the antigen-induced arthritis model. IL-6 deficiency resulted in a mild, transient inflammation whereas wild-type mice developed a chronic, destructive synovitis. Wild-type mice immunized with one-tenth of the normal antigen dose still developed chronic arthritis despite low antibody levels, excluding reduced humoral immunity in IL-6(-/-) mice as a crucial phenomenon. In addition, passive immune-complex-induced arthritis did not differ between wild-type and IL-6(-/-) mice. Another option is reduced levels of Th1 cells in IL-6(-/-) mice, However, transfer of antigen-specific wild-type lymph node cells to IL-6(-/-) mice enhanced acute joint inflammation and increased cartilage damage but still could not sustain chronic inflammation, suggesting involvement of nonimmune elements of IL-6 activity in chronicity. In line with this, nonimmunologically mediated zymosan-induced arthritis developed similarly in the first week, but only wild-type mice developed chronic synovitis. These results indicate an important role for IL-6 in propagation of joint inflammation, potentially independent of its role in immunity.