Figure 1.

Bidirectional communication between the immune system and the HPA axis. Proinflammatory cytokines, such as TNF, IL-1, and IL-6, stimulate glucocorticoid release (cortisol in humans; corticosterone in rodents) by acting at all three levels of the HPA axis (solid blue lines). In turn, glucocorticoids negatively feedback on the immune system to suppress the further synthesis and release of proinflammatory cytokines (dashed red line). In addition, glucocorticoids regulate their own production through negative feedback on the upper levels of the HPA axis, including corticotropin-releasing hormone (CRH) in the paraventricular nucleus (PVN) of the hypothalamus and adrenocorticotropin (ACTH) in the anterior pituitary (dashed red lines). Reprinted with modifications.⁹⁸