Neuro-immune interactions in the cholinergic anti-inflammatory reflex

Communication between the nervous and immune systems can significantly alter immune cell function in a number of inflammatory diseases. Elegant studies have defined a basic functional circuit in a “cholinergic anti-inflammatory pathway” that highlights a unique role for the vagus nerve, and has brought about a resurgence in the field of neuro-immunology. This research has further identified that in addition to tonic signals that can restrain immune cell activation; the anti-inflammatory reflex arc is amiable to targeted stimulation as a therapeutic modality. The success of vagal electrical neural stimulation in a plethora of pre-clinical inflammation models has spurred the development of “electroceuticals” or neurostimulatory devices in the treatment of chronic inflammation. This development has begun despite addressing of fundamental questions such as the functional neural circuitry being crudely mapped and unresolved mechanisms of action of acetylcholine on target immune cells. Perhaps fortuitously, rapid advances in neuroscience techniques may allow us to begin to answer some of these longstanding questions and clarify recent controversies.