The Cholinergic Anti-Inflammatory Pathway: A Novel Paradigm for Translational Research in Neuroimmunology

Abstract

Inflammation is a complex biologic response to gross traumatic injury, endogenous ligands, or exogenous ligands. The inflammatory response is essential for reestablishing organismal homeostasis. It must be meticulously monitored and tightly regulated as over- or under activation of the inflammatory response can cause morbidity and even mortality. Emerging evidence has begun to depict the molecular mechanisms by which inflammation is regulated via the nervous system; that is, inflammation is controlled by neuroimmunologic circuitry operating in a reflexive continuum. Known as the inflammatory reflex arc, this pathway exhibits an afferent and efferent arc: both of which derive from vagal nerve fibers. The afferent arc is comprised of vagal receptors detecting specific ligands indicating injury. An activated afferent arc will initiate the efferent arc, the cholinergic anti-inflammatory pathway, which regulates immunologically-mediated inflammation. Recent research has demonstrated that this pathway can be modulated with vagus nerve stimulation, providing a potential therapeutic option for a variety of inflammatory conditions. Here, we review the neuroimmunological mechanisms of the inflammatory reflex arc. Furthermore, we analyze current research and discuss potential therapeutic implications of the cholinergic antiinflammatory pathway.