Vagus Nerve Regulation of Inflammatory Responses in Sepsis: Mechanistic Insights and Translational Applications

The vagus nerve, often regarded as a “guardian” of physiological homeostasis, plays a pivotal role in regulating cardiovascular, neurological, and immune functions. Notably, it modulates inflammatory responses through the inflammatory reflex, a neural circuit, that involves vagal afferent sensing of peripheral inflammation and efferent regulation via the cholinergic anti-inflammatory pathway. Sepsis is a dysregulated immune disorder triggered by infection, characterized by an initial hyperinflammatory phase. In recent years, increasing attention has been directed toward harnessing vagus nerve–mediated neuromodulation to restore immune balance in sepsis. This review summarizes current insights into the mechanisms of vagus nerve–mediated inflammatory regulation, outlines two major translational strategies, and underscore the therapeutic potential of targeting vagus nerve–mediated neuroimmune pathways in sepsis.