Sensory Impairments and Delayed Regeneration of Sensory Axons in Interleukin-6-Deficient Mice
Sensory Impairments and Delayed Regeneration of Sensory Axons in Interleukin-6-Deficient Mice
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DOI：
10.1523/jneurosci.19-11-04305.1999
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发表时间：
1999-06
期刊：
影响因子：
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通讯作者：
J. Zhong;I. Dietzel;P. Wahle;M. Kopf;R. Heumann
中科院分区：
文献类型：
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作者：
J. Zhong;I. Dietzel;P. Wahle;M. Kopf;R. Heumann
白介素 6 (IL-6) 是一种介导炎症或免疫反应的多功能细胞因子。在这里，我们使用成年 IL-6 基因敲除 (IL-6−/−) 小鼠研究了 IL-6 在完整或受损周围神经系统中的可能作用。通过应用电生理学、形态学、生化和行为方法来测试各种感觉功能。与完整坐骨神经的运动分支相比，IL-6−/− 小鼠的感觉分支的复合动作电位降低了 60%。 IL-6−/− 小鼠 L5 DRG 的横截面显示神经元相对大小分布的变化。 IL-6−/−小鼠的温度敏感性也显着降低。根据行为足迹测定分析，坐骨神经挤压损伤后，IL-6−/− 小鼠的功能恢复延迟。挤压损伤后 20 天的复合动作电位测量表明，IL-6−/− 小鼠的感觉分支恢复水平非常低，但运动分支恢复水平很低。小鼠表现出缓慢的沃勒变性（Wlds）和病变诱导的巨噬细胞募集延迟，也获得了类似的感觉障碍结果。然而，与 WldS 小鼠相反，在 IL-6−/− 小鼠中，我们观察到了与 IL-6+/+ 小鼠相同的特征性病变诱导的巨噬细胞侵袭以及低亲和力神经营养蛋白受体 p75 (p75LNTR) mRNA 水平的上调。因此，导致常见感觉缺陷的机制在 IL-6−/− 和 WldS 小鼠之间是不同的。总而言之，结果表明 IL-6 对于调节体内感觉功能至关重要。
Interleukin-6 (IL-6) is a multifunctional cytokine mediating inflammatory or immune reactions. Here we investigated the possible role of IL-6 in the intact or lesioned peripheral nervous system using adult IL-6 gene knockout (IL-6−/−) mice. Various sensory functions were tested by applying electrophysiological, morphological, biochemical, and behavioral methods. There was a 60% reduction of the compound action potential of the sensory branch of IL-6−/− mice as compared with the motor branch in the intact sciatic nerve. Cross sections of L5 DRG of IL-6−/− mice showed a shift in the relative size distribution of the neurons. The temperature sensitivity of IL-6−/− mice was also significantly reduced. After crush lesion of the sciatic nerve, its functional recovery was delayed in IL-6−/− mice as analyzed from a behavioral footprint assay. Measurements of compound action potentials 20 d after crush lesion showed that there was a very low level of recovery of the sensory but not of the motor branch of IL-6−/− mice. Similar results of sensory impairments were obtained with mice showing slow Wallerian degeneration (Wlds) and a delayed lesion-induced recruitment of macrophages. However, in contrast to WldS mice, in IL-6−/− mice we observed the characteristic lesion-induced invasion of macrophages and the upregulation of low-affinity neurotrophin receptor p75 (p75LNTR) mRNA levels identical to those of IL-6+/+ mice. Thus, the mechanisms leading to the common sensory deficiencies were different between IL-6−/− and WldS mice. Altogether, the results suggest that interleukin-6 is essential to modulate sensory functions in vivo.