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.