title: Neuroimmune Control of Acute Kidney Injury and Inflammation.
abstract: Despite major advances in identifying pathophysiological mechanisms of acute kidney injury (AKI), no definitive therapeutic or preventive modalities have been developed with the exception of dialysis. One possible approach is the control of inflammation and AKI through activation of the neuroimmune axis. The cholinergic anti-inflammatory pathway is thought to contribute to the homeostatic response in inflammation-related disorders and forms the basis for recent approaches toward therapeutic intervention. The concept is based on the emerging understanding of the interface between the nervous and immune systems. In the cholinergic anti-inflammatory pathway, the efferent vagus nerve indirectly stimulates the CD4+ T-cells in the spleen. The CD4+ T-cells produce acetylcholine, which stimulates alpha 7 nicotinic receptors (α7nAChRs) on macrophages. Activation of the α7nAChRs on macrophages in turn activates NF-x03BA;β and elicits an anti-inflammatory response. Recently, we demonstrated the effect of a non-pharmacologic, noninvasive, ultrasound-based method to prevent renal ischemia-reperfusion injury and sepsis-induced AKI in mice. Our data suggest that ultrasound-induced tissue protection is mediated through the activation of the cholinergic anti-inflammatory pathway. In addition, nicotinic receptor agonists and ghrelin, a neuropeptide, were reported to prevent AKI possibly through a mechanism closely linked with the stimulation of the vagus nerve. Based on the studies focusing on inflammation and the observations regarding kidney injury, we believe that activating the cholinergic anti-inflammatory pathway will be a new modality for the prevention and treatment of AKI.
authors.affiliation: Department of Medicine, Division of Nephrology and Center for Immunity, Inflammation, and Regenerative Medicine, University of Virginia Health System, Charlottesville, Va., USA.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Mark D
authors.initials: MD
authors.lastname: Okusa
mesh_terms: D058186:Acute Kidney Injury / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D001341:Autonomic Nervous System / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D051379:Mice; D015213:Neuroimmunomodulation / Q000276:immunology*; D014630:Vagus Nerve / Q000276:immunology / Q000503:physiopathology