Exploring the Potential Role of the Cholinergic Anti-Inflammatory Pathway from the Perspective of Sepsis Pathophysiology

Sepsis is one of the most prevalent conditions in critical care medicine and is characterized by a high incidence, mortality, and poor prognosis, with no specific treatment currently available. The pathogenesis of sepsis is complex with a dysregulated inflammatory response at its core. If the initial inflammatory response is not promptly controlled, patients often develop multiple organ dysfunction syndrome or die, whereas survivors may experience post-sepsis syndrome. Regulation by the central and autonomic nervous systems is essential for maintaining inflammatory homeostasis. Among these, the cholinergic anti-inflammatory pathway (CAP) has been extensively studied in sepsis owing to its significant role in modulating inflammatory responses. Recent advancements in CAP-related interventions include minimally invasive vagus nerve stimulation, novel α7nAchR-targeting drugs, serum choline acetyltransferase and cholinesterase, acupuncture, and focused ultrasound stimulation therapy. This review primarily discusses the advantages, limitations, and therapeutic prospects of these approaches. Additionally, heart rate variability, which reflects changes in autonomic nervous system function, can serve as an indicator for assessing the functional status of the vagus nerve. In summary, modulation of inflammatory responses through the vagus nerve-mediated CAP represents a potential strategy for achieving precision medicine for sepsis. Future research should focus on conducting high-quality clinical studies on CAP-based therapies in the context of sepsis-induced inflammatory dysregulation. Incorporating indicators to evaluate the autonomic nervous system function may further elucidate the impact of inflammatory dysregulation in the body.