Vagus Nerve-Mediated Immunity

The capacity for the vagus nerve to regulate immune-homeostasis has been a focus of laboratory studies based on the significant insights into how stimulation of the vagus nerve can mediate the inflammatory setpoint in injury. Injury setpoint refers to the systemic inflammatory status either pre-/post-injury or during the course of care that may alter the immune response and account for different outcomes between individuals who suffer similar injuries. Studies in our laboratory have defined the ability of vagal nerve stimulation (VNS) to prevent intestinal inflammation and improve gut epithelial barrier function after injury. Intestinal inflammation following injury has previously been defined as the catalyst for the systemic inflammatory response to injury that can lead to organ failure and late deaths in injured patients. Our studies have identified enteric glia cells, a component of the enteric nervous system, as a candidate cell type that may mediate the gut protective effects of VNS. By harnessing the anti-inflammatory effects of enteric glia cell activation, we hope to develop therapeutics that may improve outcomes in patients following severe trauma and burn injury.

Publication Highlights

Costantini TW, Krzyzaniak M, Cheadle GA, Putnam JG, Hageny AM, Lopez N, Eliceiri BP, Bansal V, Coimbra R. Targeting α-7 nicotinic acetylcholine receptor in the enteric nervous system: A cholinergic agonist prevents gut barrier failure after severe burn injury. Am J Pathol 2012 Aug;181(2):478-86. Epub 2012 Jun 8.

Costantini TW, Bansal V, Krzyzaniak MJ, Putnam JG, Peterson CY, Loomis WH, Wolf PL, Baird A, Eliceiri BP, Coimbra R. Vagal nerve stimulation protects against burn-induced intestinal injury through activation of enteric glia cells. Am J Physiol Gastrointest Liver Physiol 2010 Dec;299(6):G1308-18. Epub 2010 Aug 12.

Lopez NE, Krzyzaniak M, Costantini TW, De Maio A, Baird A, Eliceiri BP, Coimbra R. Vagal Nerve Stimulation Blocks Peritoneal Macrophage Inflammatory Responsiveness After Severe Burn Injury. Shock 2012 Aug;38(3):294-300. PMCID: PMC3422402.

Krzyzaniak MJ, Peterson CY, Cheadle G, Loomis W, Wolf P, Kennedy V, Putnam JG, Bansal V, Eliceiri B, Baird A, Coimbra R. Efferent vagal nerve stimulation attenuates acute lung injury following burn: The importance of the gut-lung axis. Surgery 2011 Sept; 150(3):379-89. Epub 2011 Jul 23.

Costantini TW, Bansal V, Peterson CY, Loomis WH, Putnam JG, Rankin F, Wolf P, Eliceiri BP, Baird A, Coimbra R. Efferent vagal nerve stimulation attenuates gut barrier injury after burn: modulation of intestinal occludin expression. J Trauma 2010 Jun;68(6):1349-54; discussion 1354-6.

Lopez N, Krzyzaniak M, Chelsea B, Ortiz-Pomales Y, Hageny AM, Eliceiri B, Coimbra R, Bansal V. Ghrelin prevents disruption of the blood brain barrier after traumatic brain injury. Journal of Neurotrauma 2012 Jan 20;29(2):385-93. Epub 2011 Oct 26.