Divergent neuroendocrine responses to localized and systemic inflammation

• Infection and inflammation can affect afferent neurons in the periphery, integrative autonomic centers in the brain and neuroendocrine cells, including adrenal chromaffin cells (ACCs).
• Catecholamines released from postganglionic sympathetic neurons and ACC can suppress immune system activation.
• Models of localized gastrointestinal inflammation are associated with inhibition of ACCs whereas endotoxemia leads to elevation of catecholamine release from ACCs.
• These differential effects are likely due to direct effects of circulating inflammatory mediators on ACCs.

The sympathetic nervous system (SNS) is part of an integrative network that functions to restore homeostasis following injury and infection. The SNS can provide negative feedback control over inflammation through the secretion of catecholamines from postganglionic sympathetic neurons and adrenal chromaffin cells (ACCs). Central autonomic structures receive information regarding the inflammatory status of the body and reflexively modulate SNS activity. However, inflammation and infection can also directly regulate SNS function by peripheral actions on postganglionic cells. The present review discusses how inflammation activates autonomic reflex pathways and compares the effect of localized and systemic inflammation on ACCs and postganglionic sympathetic neurons. Systemic inflammation significantly enhanced catecholamine secretion through an increase in Ca2+ release from the endoplasmic reticulum. In contrast, acute and chronic GI inflammation reduced voltage-gated Ca2+ current. Thus it appears that the mechanisms underlying the effects of peripheral and systemic inflammation neuroendocrine function converge on the modulation of intracellular Ca2+ signaling.