Background

The glucocorticoid receptor (GR) plays a role in inflammatory pain modulation. However, the specific role played by interleukin 6 receptor (IL-6R) in these processes remains elusive. The present study aimed to investigate the extent of inflammation induced by IL-6R and GR.

Methods

Male Wistar rats were treated with Freund’s complete adjuvant to induce right hind paw inflammation. The levels of IL-6Rα and GR were evaluated in the spinal cord and dorsal root ganglion using Western blot and immunofluorescence assays. Subsequently, we examined the nociceptive behavioral changes following the binding of IL-6R with a GR agonist and/or antagonist, as well as the concentration levels of IL-6 and soluble IL-6R (sIL-6R) in the serum and cerebrospinal fluid. Moreover, the spinal levels of IL-6, IL-6Rα, gp130, JAK2, pJAK2, STAT3, pSTAT3, c-fos, GFAP, and Iba-1 were assessed following anti-IL-6R antibody, sgp130, and dexamethasone intrathecal administration.

Results

Right hind paw inflammation resulted in significant upregulation of IL-6Rα expression in spinal nociceptive neurons, astrocytes, and microglia cells, as well as increased of IL-6Rα and GR colocalization. Notably, anti-IL-6R or dexamethasone attenuated the nociceptive behavior in a dose-dependent manner. Isobologram analysis indicated the sub-additive effects with a concomitant decrease in the spinal levels of IL-6, pJAK2, pSTAT3, c-fos, GFAP, and Iba-1 and increase in the sIL-6R level.

Conclusion

The enhanced mechanical sensitivity accompanying the increase of IL-6Rα and GR was attenuated by anti-IL-6R and dexamethasone application, and the sub-additive effects were regulated by the decreased activation of neurons and glial cells and modulated by IL-6/JAK2/STAT3 signaling pathway, which might be attributed to IL-6 induced trans-signaling.

中文翻译：

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IL-6R对糖皮质激素受体在大鼠后爪炎性疼痛中的镇痛作用。

背景

糖皮质激素受体（GR）在炎症性疼痛调节中起作用。但是，白介素6受体（IL-6R）在这些过程中所起的特定作用仍然难以捉摸。本研究旨在调查由IL-6R和GR引起的炎症程度。

方法

用弗氏完全佐剂处理雄性Wistar大鼠，以诱导右后爪发炎。使用蛋白质印迹法和免疫荧光法评估脊髓和背根神经节中IL-6Rα和GR的水平。随后，我们检查了IL-6R与GR激动剂和/或拮抗剂结合后的伤害性行为变化，以及血清和脑脊液中IL-6和可溶性IL-6R（sIL-6R）的浓度水平。此外，在鞘内给药抗IL-6R抗体，sgp130和地塞米松后，评估了IL-6，IL-6Rα，gp130，JAK2，pJAK2，STAT3，pSTAT3，c-fos，GFAP和Iba-1的脊髓水平。

结果

右后爪发炎导致脊髓伤害感受神经元，星形胶质细胞和小胶质细胞中IL-6Rα表达的显着上调，以及IL-6Rα和GR共定位的增加。值得注意的是，抗IL-6R或地塞米松以剂量依赖性方式减弱了伤害性行为。等效线图分析表明，亚加性作用伴随着IL-6，pJAK2，pSTAT3，c-fos，GFAP和Iba-1的脊髓水平降低，而sIL-6R水平升高。

结论

抗IL-6R和地塞米松的应用会减弱伴随IL-6Rα和GR升高而增强的机械敏感性，而亚加成作用则受神经元和神经胶质细胞激活减少的调节，并受IL-6 / JAK2的调节。 / STAT3信号传导途径，可能归因于IL-6诱导的反信号传导。