The prevailing notion has been that cytokines such as interleukin-1 released from sites of
inflammation cross the blood–brain barrier and drive the hypothalamo–pituitary–adrenal
(HPA) axis so that cortisol is released into the circulation to exert indiscriminate systemic anti-
inflammatory effects. It is now clear that feedback from the HPA axis is subject to more subtle
and localized regulation. The signal that activates cortisol release travels to the
hypothalamus via vagal sensory afferents (so the brain 'knows' where the inflammation is) …