Vagal Modulation of the Inflammatory Response in Sepsis

The vagus nerve can sense peripheral inflammation and transmit action potentials from the periphery to the brainstem. Vagal afferent signaling is integrated in the brainstem, and efferent vagus nerves carry outbound signals that terminate in spleen and other organs. Stimulation of efferent vagus nerve leads to the release of acetylcholine in these organs. In turn, acetylcholine interacts with members of the nicotinic acetylcholine receptor (nAChR) family, particularly with the alpha7 nicotinic acetylcholine receptor (α7nAChR), which is expressed by macrophages and other cytokine-producing cells. Ultimately, the production of proinflammatory cytokines is markedly inhibited. This neuroimmune communication is termed "the inflammatory reflex". The uncontrolled inflammation as a result from sepsis can lead to multiple organ failure, and even death. Experimental data show that regulation of the inflammatory reflex appears to be a useful interventional strategy for septic response. Herein, we review recent advances in the understanding of the inflammatory reflex and discuss potential therapeutics that vagal modulation of the immune system for the treatment of severe sepsis and septic shock.