Figure 3. Functional anatomy of the inflammatory reflex.
Afferent (sensory) neural signals to the brain stem are relayed by the vagus nerve to the nucleus of the solitary tract (nucleus tractus solitarius; NTS). Polysynaptic relays then connect to the outflow centres of the autonomic nervous system, the rostral ventrolateral medullary (RVLM) sympathoexcitatory neurons and the vagal motor neurons in the nucleus ambiguus (NA) and the dorsal vagal motor nucleus. Outflow arrives at the coeliac ganglion from either the vagus nerve or the preganglionic efferent nerves, which originate in the sympathetic trunk. Stimulating the vagus nerve suppresses innate immune responses and downregulates pro-inflammatory cytokine release in the spleen through a mechanism that depends on nicotinic acetylcholine receptor subunit α7 (α7nAChR). Note that, following the activation of the inflammatory reflex by sensory input to the brainstem, the signals are also relayed to the nuclei controlling the function of the hypothalamic–pituitary-–adrenal (HPA) axis, which increases glucocorticoid hormone release by the adrenal gland. This provides an important connection between the neural networks that can acutely provide compensatory signals to adjust immune responses, and the humoral anti-inflammatory mechanisms that can more chronically modulate innate and adaptive immune responses. The identity and mechanism of function of the set point centre is unknown. It establishes the magnitude of the set function of immune output around which compensatory reflex responses maintain homeostasis.