Dual role of interleukin-10 in murine lyme disease: Regulation of arthritis severity and host defense
Dual role of interleukin-10 in murine lyme disease: Regulation of arthritis severity and host defense
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DOI：
10.1128/iai.67.10.5142-5150.1999
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发表时间：
1999-10-01
影响因子：
3.1
通讯作者：
Wooten, RM
中科院分区：
文献类型：
--
作者：
Brown, JP;Zachary, JF;Wooten, RM
在莱姆病的鼠模型中，当感染伯氏疏螺旋体时，C3 H/He小鼠表现出严重的关节炎，而C57 BL/6 N小鼠表现出轻度病变。来自这两种小鼠品系的关节组织具有相似的B浓度。burgdorferi，表明疾病严重程度的差异反映了对B的炎症反应程度的差异。伯氏脂蛋白用B刺激来自C3 H/HeN小鼠的骨髓巨噬细胞。与C57 BL/6 N小鼠的巨噬细胞相比，Burgdorferi脂蛋白OspA导致炎症介质肿瘤坏死因子α、一氧化氮和白细胞介素-6（IL-6）的产生水平更高。相比之下，来自C57 BL/6 N小鼠的巨噬细胞始终产生比C3 H/HeN巨噬细胞更大量的抗炎细胞因子IL-10。添加重组IL-10抑制两种菌株巨噬细胞产生炎症介质。发现IL-10调节B。由于IL-10缺陷型（IL-10（-/-））C57 BL/6 J螨比野生型C57 BL/6 J小鼠发展出更严重的关节炎，因此，在体内，C57 BL/6 J螨诱导了炎症。关节炎严重程度的增加与B数量的10倍减少有关。来自IL-10（-/-）小鼠的踝部组织中存在的伯氏菌。这些发现表明，在C57 BL/6小鼠中，IL-10依赖性调节关节炎严重程度是以牺牲有效控制细菌数量为代价的。
In the murine model of Lyme disease, C3H/He mice exhibit severe arthritis while C57BL/6N mice exhibit mild lesions when infected with Borrelia burgdorferi. Joint tissues from these two strains of mice harbor similar concentrations of B. burgdorferi, suggesting that the difference in disease severity reflects differences in the magnitude of the inflammatory response to B. burgdorferi lipoproteins. Stimulation of bone marrow macrophages from C3H/HeN mice with the B. burgdorferi lipoprotein OspA resulted in higher-level production of the inflammatory mediators tumor necrosis factor alpha, nitric oxide, and interleukin-6 (IL-6) than that of macrophages from C57BL/6N mice. In contrast, macrophages from C57BL/6N mice consistently produced larger amounts of the anti-inflammatory cytokine IL-10 than did C3H/HeN macrophages. Addition of recombinant IL-10 suppressed the production of inflammatory mediators by macrophages from both strains. IL-10 was found to modulate B. burgdorferi-induced inflammation in vivo, since C57BL/6J mite deficient in IL-10 (IL-10(-/-)) developed more severe arthritis than wild-type C57BL/6J mice. The increase in arthritis severity was associated with a 10-fold decrease in the number of B. burgdorferi organisms present in ankle tissues from IL-10(-/-) mice. These findings suggest that in C57BL/6 mice, IL-10-dependent regulation of arthritis severity occurs at the expense of effective control of bacterial numbers.