Authors: Abdulaziz Almanea

Abstract

Background: The nervous and immune systems are intricately connected and engage in continuous bidirectional communication that is essential for maintaining physiological homeostasis. Recent advances have highlighted the pivotal role of the vagus nerve in the modulation of immune responses via the cholinergic anti-inflammatory pathway. This narrative review explores the mechanisms and clinical implications of vagus nerve stimulation (VNS) in regulating immune function, focusing on inflammatory and autoimmune diseases, pain modulation, and emerging applications in conditions such as COVID-19.
Methods: A comprehensive literature search was conducted using PubMed, Google Scholar, and Scopus to identify relevant preclinical and clinical studies of VNS and immunomodulation. Studies were selected on the basis of their relevance to neuro-immune communication, inflammatory markers, and clinical outcomes.
Results: Evidence from animal models and human trials demonstrates that VNS can reduce pro-inflammatory cytokines (e.g., TNF-α and IL-6), enhance anti-inflammatory mediators (e.g., IL-10), and improve disease outcomes in sepsis, rheumatoid arthritis, cardiovascular disease, diabetes, and chronic pain. Non-invasive VNS also has the potential to modulate immune responses in COVID-19. The psychoneuroimmunological perspective emphasizes the influence of neural activity and psychological stress on immune regulation.
Conclusion: VNS offers a novel and minimally invasive strategy for modulating immune function in a spectrum of diseases characterized by chronic inflammation and autonomic imbalance. As research progresses, stimulation protocols have been optimized. Expanding clinical trials will be key to fully realizing the therapeutic potential of neuro-immune modulation. 

Keywords: Neuroimmune cross talking, VNS, Immunomodulation, Cholinergic Anti-inflammatory Pathway.