Neuroimmunomodulation of tissue injury and disease: an expanding view of the inflammatory reflex pathway

Neuroimmunomodulation through peripheral nerve activation is an important therapeutic approach to various disorders. Central to this approach is the inflammatory reflex pathway in which the cholinergic anti-inflammatory pathway represents the efferent limb. Recent studies provide a framework for understanding this control pathway, however our understanding remains incomplete. Genetically modified mice, using optogenetics and pharmacogenomics, have been invaluable resources that will allow investigators to disentangle neural pathways that provide a unifying mechanism by which vagal nerve stimulation (and other means of stimulating the pathway) leads to an anti-inflammatory and tissue protective effect. In this review we describe disease models that contribute to our understanding of how vagal nerve stimulation attenuates inflammation and organ injury: acute kidney injury, rheumatoid arthritis, and inflammatory gastrointestinal disease. The gut microbiota contributes to health and disease and the potential role of the vagus nerve in affecting the relationship between gut microbiota and the immune system and modifying diseases remains an intriguing opportunity to attenuate local and systemic inflammation that undergird disease processes.