Engaging Brain Anti-inflammatory Circuits to Improve the Viability of Transplanted Organs

Solid organ transplantation is a life-saving intervention for tens of thousands of patients each year in the United States. A major underlying pathophysiologic process limiting the success of transplantation is inflammation. Since the first transplant >70 y ago, advancements in the fields of surgery and immunosuppression have improved both organ and patient survival. However, inflammation and its damaging effects remain the principal clinical problem limiting enduring organ transplant survival. The discovery of the vagus nerve-mediated inflammatory reflex, an endogenous mechanism attenuating inflammatory processes, has provided novel treatment approaches for patients with autoimmune, neurologic, gastrointestinal, and other immune-mediated disorders. Despite these successes, evaluation of whether the inflammatory reflex can improve graft and patient survival in transplantation has yet to be undertaken. Here, we review the fundamentals of transplant rejection and how the inflammatory reflex may provide potential preemptive therapy in deceased donors before organ recovery, as well as attenuate detrimental inflammatory processes in transplant recipients. With this background, we propose that vagus nerve stimulation could be used to improve organ viability and augment current immunosuppressive medication regimens, thereby improving transplantation outcomes.