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. 2014 Oct 13;20(1):1–10. doi: 10.1179/1351000214Y.0000000107

Figure 2.

Figure 2.

HPA-axis in response to LPS and cross-talk between the brain and immune system: The major part of the HPA-axis system is constituted by the hypothalamus, the pituitary gland, and the adrenal glands. When exposed to stressors, secretion of corticotropin-releasing factor (CRF) into hypophysial portal vessels stimulates the anterior pituitary gland thereby releasing adrenocorticotropic hormone (ACTH) into the circulation. Circulating ACTH binds to the type-2 melanocortin receptor (MC2R) in the adrenal cortex, where it stimulates glucocorticoid release. Elevated glucocorticoids in the circulation inhibit further activation of the HPA-axis through glucocorticoid receptor-mediated mechanisms in the brain so as to maintain homeostasis. Invading pathogens enhance glucocorticoid release that modulates the systemic immune response. TLR4-stimulated immune cells in response to LPS release excessive amounts of cytokines into the circulation, thereby stimulating the HPA-axis. In addition, LPS directly affects activation of the HPA-axis via the TLR4 signaling pathway exhibited in both the resident immune cells and neurons in the brain. Blue lines represent the HPA-axis to maintain homeostasis; blue dotted lines represent suppression of glucocorticoid release by negative feedback loops; red lines represent stimulation of the HPA-axis in response to LPS.