[Research progress on the potential mechanisms and effects of the cholinergic anti-inflammatory pathway in sepsis]

Sepsis is a common clinical syndrome in intensive care unit (ICU) with high morbidity and high mortality, making it a global health issue. The estimated global incidence of sepsis is 437/100 000, with an in-hospital mortality of 17%, which is higher in developing countries and underdeveloped regions. Despite some progress in sepsis treatment in recent years, the complexity of its pathophysiology limits therapeutic effectiveness. The cholinergic anti-inflammatory pathway (CAP), a neuro-immune regulatory pathway, plays a crucial role in sepsis through key components such as the vagus nerve, central M-type muscarinic receptor, the spleen and splenic sympathetic nerves, acetylcholine, and the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR). This article explores the potential mechanisms and roles of CAP in sepsis, focusing on CAP-related cell signaling pathways, including nuclear factor-κB (NF-κB) signaling pathway, Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, and cyclooxygenase (COX) and prostaglandin E2 (PGE2) signaling pathways. Potential applications of CAP in sepsis treatment include stimulating the vagus nerve (e.g., through pharmacological, electrical, or acupuncture stimulation), using α7nAChR agonists (e.g., nicotine, GTS-21, and PNU-282987), adrenergic receptor agonists (e.g., dexmedetomidine and salbutamol), or other drugs and bioactive substances (e.g., buprenorphine and traditional Chinese medicine components). These approaches aim to activate CAP, suppress inflammatory responses, and improve sepsis prognosis, providing a theoretical basis for treatment and promoting the development of related drugs.