Fig. 1

Neuronal reflexes controlling inflammation. The HPA axis is activated by several stimuli to activate the paraventricular nucleus (PVN) of the hypothalamus leading to the release of cortisol releasing hormone (CRH) into the anterior pituitary. In turn, CRH induces the release of adrenocorticotrophic hormone (ACTH) in blood, which stimulate the production of glucocorticoids (GC) by the cortex of the adrenal glands, which are potent anti-inflammatory molecules whose effect is mediated by the signaling via glucocorticoid receptor (GR), a nuclear receptor expressed by almost all cells in the body and in particular in innate immune cells; Vagal anti-inflammatory reflex is characterized by peripheral vagal afferent nerves detecting inflammation and sending this information to the CNS. Reciprocal connections between the NTS and DMN mediate communication with and activation of efferent vagus nerve fibers inducing the release of ACh and ultimately attenuating cytokine production and inflammation through a mechanism, based on the binding of ACh on nicotinic α7nAChR; Additionally, these cytokines can also activate directly this region in the brain by a humoral control in order to revert inflammation; Sympathetic fibers originating in the spinal cord terminate innervate directly visceral organs and immune cells and release norepinephrine (NE) that binds to its specific receptors on these cells. Efferent sympathetic output to the adrenal gland induces the secretion of epinephrine (EP) from chromaffin cells that circulates in blood to reach specific receptors in immune cells. EN and NE joint action stops inflammation and release of inflammatory cytokines; finally, inflammation resolution also occurs through carotid body (CB) action. Briefly, released inflammatory mediators by immune cells activate the CB, which in turn activates carotid sinus nerve (CSN) that projects within the nucleus tractus solitarii (NTS)