BackgroundRenal denervation (RDN) reduces sympathetic tone and may alter the sympathetic-parasympathetic balance. The autonomic nervous system is partly a regulator of innate immunity via the cholinergic anti-inflammatory pathway (CAP) which inhibits inflammation via the vagus nerve. Placental Growth Factor (PlGF) influences a neuro-immunological pathway in the spleen which may contribute to hypertension. The aim of this study was to investigate if modulation of renal sympathetic nerve activity affects CAP in terms of cytokine release as well as levels of PlGF.MethodsTen patients treated with RDN (Medtronic Inc), were analyzed for TNF, IL-1b and IL-10 and Lipopolysaccharide (LPS)-stimulated cytokine release before RDN, 1 day after and at 3- and 6-months follow-up. Four patients who underwent elective coronary angiography served as disease controls (DC).ResultsBaseline TNF was significantly lower 1 day after RDN (p = 0.03). LPS-stimulated (0, 10 and 100 ng/mL) TNF and IL-1b were significantly lower 1 day after RDN (TNF p = 0.0009, p = 0.0009 and p = 0.001, IL-1b; p = 0.0001, p = 0.002 and p = 0.005). IL-10 was significantly higher one day after RDN (p = ns, p = 0.02 and p = 0.01). These differences however declined during follow up. A more marked TNF reduction was achieved with a cholinergic analogue, GTS-21, in LPS-stimulated whole blood as compared with samples without GTS-21. Cytokine levels in controls did not differ before and 1 day after coronary angiography. PlGF was significantly higher in RDN patients and DC compared with healthy controls but did not change during follow-up.ConclusionRDN has an immediate effect on TNF in vivo and cytokine release ex vivo but seems to wane over time suggesting that current RDN techniques may not have long-lasting immunomodulatory effect. Repeated and extended stimulation of CAP in resistant hypertension by targeting neural circuits may be a potential therapeutic strategy for treatment of both hypertension and inflammation.

中文翻译：

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肾去神经支配治疗顽固性高血压的胆碱能抗炎通路

背景去肾神经支配 (RDN) 会降低交感神经张力并可能改变交感神经-副交感神经平衡。自主神经系统在一定程度上是通过胆碱能抗炎通路 (CAP) 调节先天免疫的，该通路通过迷走神经抑制炎症。胎盘生长因子 (PlGF) 影响脾脏中的神经免疫通路，这可能导致高血压。本研究的目的是研究肾交感神经活动的调节是否会在细胞因子释放和 PlGF 水平方面影响 CAP。方法 分析了 10 名接受 RDN（美敦力公司）治疗的患者的 TNF、IL-1b 和 IL- 10 和脂多糖 (LPS) 刺激的细胞因子在 RDN 之前、之后 1 天和 3 个月和 6 个月的随访中释放。4 名接受选择性冠状动脉造影的患者作为疾病对照（DC）。结果 RDN 后 1 天基线 TNF 显着降低（p = 0.03）。LPS 刺激（0、10 和 100 ng/mL）TNF 和 IL-1b 在 RDN 后 1 天显着降低（TNF p = 0.0009，p = 0.0009 和 p = 0.001，IL-1b；p = 0.0001，p = 0.002和 p = 0.005）。RDN 后一天 IL-10 显着升高（p = ns，p = 0.02 和 p = 0.01）。然而，这些差异在随访期间有所下降。与不含 GTS-21 的样品相比，在 LPS 刺激的全血中，使用胆碱能类似物 GTS-21 可实现更显着的 TNF 降低。在冠状动脉造影术之前和之后 1 天，对照组中的细胞因子水平没有差异。与健康对照相比，RDN 患者和 DC 的 PlGF 显着更高，但在随访期间没有变化。结论 RDN 对体内 TNF 和离体细胞因子释放具有直接影响，但似乎随着时间的推移而减弱，表明当前的 RDN 技术可能没有持久的免疫调节作用。通过靶向神经回路对顽固性高血压患者的 CAP 重复和延长刺激可能是治疗高血压和炎症的潜在治疗策略。