Heart failure (HF) is characterized by autonomic nervous system (ANS) imbalance and low-grade chronic inflammation. The bidirectional relationship between the ANS and immune system (IS) is named “neuroimmune cross-talk” (NICT), and is based on common signaling molecules, receptors, and pathways. NICT may be altered in HF, and neuroinflammation seems to be a main driver of HF progression. In HF, heightened sympathetic nerve activity triggers inflammatory cascades that lead to cardiomyocyte death and myocardial interstitial fibrosis. Concurrently, parasympathetic withdrawal may impair the cholinergic anti-inflammatory pathway, with a less effective immune response to infections or inflammatory events. Additionally, microglial activation and inflammatory molecules contribute to autonomic imbalance by acting on central nuclei and peripheral visceral feedbacks, which in turn promote adverse cardiac remodeling, HF decompensation, and potentially life-threatening arrhythmias. Therefore, neuroinflammation has been identified as a potential target for treatment. Pharmacological antagonism of the neurohormonal system remains the cornerstone of chronic HF therapy. While some drugs used in HF management may have additional benefits due to their anti-inflammatory properties, clinical trials targeting inflammation in patients with HF have so far produced inconclusive results. Nevertheless, considering the pathophysiological relevance of NICT, its modulation seems an appealing strategy to optimize HF management. Current research is therefore investigating novel pharmacological targets for anti-inflammatory drugs, and the immunomodulatory properties of denervation approaches and bioelectronic medicine devices targeting NICT and neuroinflammation in HF. A deeper understanding of the complex relationship between the ANS and IS, as outlined in this review, could therefore facilitate the design of future studies aimed at improving outcomes by targeting NICT in patients with HF.

中文翻译：

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心力衰竭中的神经免疫串扰


心力衰竭 （HF） 的特征是自主神经系统 （ANS） 失衡和低度慢性炎症。ANS 和免疫系统 （IS） 之间的双向关系称为“神经免疫串扰”（NICT），基于常见的信号分子、受体和通路。NICT 在 HF 中可能发生改变，神经炎症似乎是 HF 进展的主要驱动因素。在 HF 中，交感神经活动增强会触发炎症级联反应，导致心肌细胞死亡和心肌间质纤维化。同时，副交感神经戒断可能会损害胆碱能抗炎途径，对感染或炎症事件的免疫反应效果较差。此外，小胶质细胞活化和炎症分子通过作用于中央核和外周内脏反馈而导致自主神经失衡，这反过来又促进了不良的心脏重塑、HF 失代偿和可能危及生命的心律失常。因此，神经炎症已被确定为潜在的治疗靶点。神经激素系统的药物拮抗作用仍然是慢性 HF 治疗的基石。虽然一些用于 HF 管理的药物由于其抗炎特性可能具有额外的益处，但针对 HF 患者炎症的临床试验迄今尚未产生定论结果。然而，考虑到 NICT 的病理生理相关性，其调节似乎是优化 HF 管理的有吸引力的策略。因此，目前的研究正在调查抗炎药的新型药理学靶点，以及针对 NICT 和 HF 神经炎症的去神经支配方法和生物电子医学装置的免疫调节特性。 因此，如本综述所述，更深入地了解 ANS 和 IS 之间的复杂关系，可以促进未来研究的设计，旨在通过靶向 HF 患者的 NICT 来改善结局。