聚焦超声刺激（FUS）可激活机感性离子通道，逐渐成为一种无创神经调控方法。在临床前研究中，脾脏的FUS（sFUS）激活了一种抗炎神经途径，可抑制急性和慢性炎症。然而，对于sFUS对人体炎症反应的调节作用尚不清楚。本研究使用一种改进的诊断超声成像系统，在人类健康受试者的脾脏中定位三分钟连续扫描或静态聚焦脉冲超声，分别在允许安全曝光限制内的三个不同能量水平下进行。通过测量受超声照射的受试者的全血样本中，sFUS引发的内毒素诱导肿瘤坏死因子（TNF）生产的变化，评估了sFUS的潜在抗炎作用。我们发现，使用连续扫描或聚焦脉冲超声都具有抗炎作用：sFUS可降低TNF的产生超过2小时，而TNF在sFUS后24小时内恢复到基线。这种反应与解剖靶点（即脾门或实质）或超声能量水平无关。不会对临床、生化或血液学参数产生不良影响。这是首次证明sFUS抑制了人体正常的炎症反应，具有非侵入性的生物电疗法治疗炎症疾病的潜在意义。版权所有©2023 Elsevier Inc.发表。

Focused ultrasound stimulation (FUS) activates mechanosensitive ion channels and is emerging as a method of noninvasive neuromodulation. In preclinical studies, FUS of the spleen (sFUS) activates an anti-inflammatory neural pathway which suppresses acute and chronic inflammation. However, the relevance of sFUS for regulating inflammatory responses in humans is unknown. Here, we used a modified diagnostic ultrasound imaging system to target the spleen of healthy human subjects with 3 minutes of continuously swept or stationary focused pulsed ultrasound, delivered at three different energy levels within allowable safety exposure limits. Potential anti-inflammatory effects of sFUS were assessed by measuring sFUS-elicited changes in endotoxin-induced tumor necrosis factor (TNF) production in whole blood samples from insonified subjects. We found that stimulation with either continuously swept or focused pulsed ultrasound has an anti-inflammatory effect: sFUS lowers TNF production for >2 hours, with TNF returning to baseline by 24 hours following sFUS. This response is independent of anatomical target (i.e., spleen hilum or parenchyma) or ultrasound energy level. No clinical, biochemical, or hematological parameters are adversely impacted. This is the first demonstration that sFUS suppresses the normal inflammatory response in humans, with potential implications for noninvasive bioelectronic therapy of inflammatory disorders.Copyright © 2023. Published by Elsevier Inc.