In periventricular nucleus, initiating the HPA pathway.
In response to chronic stressors, thehypothalamus releases corticotropin-releasing hormone (CRH) from theperiventricular nucleus, initiating the HPA pathway. CRH stimulates thepituitary gland to release adrenocorticotropic hormone (ACTH), which enters thecirculation and ultimately stimulates the cortex of the adrenal glands toproduce glucocorticoids, of which cortisol is the primary stress hormone inhumans. Dehydroepiandrosterone (DHEA) is also released, which is an endogenoushormone that regulates the activity of cortisol.
A parallel pathway, the Sympathoadrenalmedullary (SAM) axis activation, results from the sympathetic innervation ofthe adrenal gland’s medulla, which in turn results in the release of adrenal Catecholamines(adrenaline and noradrenaline). All biochemical mediators, glucocorticoids,DHEA and Catecholamines can each independently alter immune function.Generally, cortisol is an immunosuppressant, known to have strong effects on helperT cells type 1 (Th1) and type 2 (Th2) (Chen 2007) responses, through inhibiting the production ofIL-12, a major inducer of Th1 responses, by antigen-presenting cells, resultingin decreased Th1 cell-derived interferon (IFN)-? and increased production of the TH2 cytokines IL-4,IL-10 and IL-13. As a result, cortisol enhances Th2 functions, such as theproduction of immunoglobulins. Whenever the body isexposed to stress, the physiological system responds by stimulating thehypothalamus which results in the secretion of Corticotrophin releasing hormone(CRH). This is released into the Hypophyseal portal system, activating thepituitary gland to release adrenocorticotropic hormone (ACTH), which in turninduces the release of corticosteroids from the adrenal cortex. Glucocorticoids,including cortisol (the primary glucocorticoid), exert major suppressiveeffects through highly specific mechanisms at different levels.
At themolecular level, they inhibit vital functions of inflammatory cells includingmacrophages, neutrophils, eosinophils, and mast cells in functions such asChemotaxis, secretion, and degranulation. The immune response cascade is alsoaffected as cortisol inhibits the macrophage-antigen presentation, lymphocyteproliferation, and lymphocyte differentiation to effector cell types such ashelper lymphocytes, cytotoxic lymphocytes, natural killer cells, andantibody-forming B cells. Corticosteroids also inhibit the production ofcytokines including IL-1, IL-2, IL-3, and IL-6, tumour necrosis factor,interferon gamma, and granulocyte and monocyte colony stimulating factors.Glucocorticoids inhibit arachidonic acid-derived pro-inflammatory mediators,anti-inflammatory proteins and lipocortins, and finally inhibit the generationof eicosanoids. Therefore, thestress-related stimulation of the HPA suppress immune and inflammatoryresponses. Other peripherally generatedinflammatory mediators that can activate the HPA axis includelymphocyte-derived gamma Interferon, IL-2, IL-6, macrophage-derived IL- 1, andtumour necrosis factors
