Immune system cortisol

The increased disease susceptibility associated with the stress response is not solely mediated through the immune system. Cortisol also impairs healing of epithelium (Roubal Bullock, 1988 Johnson Albright, 1992) and the stress response can lead to changes in behaviour. The nature of the association between stressors and disease susceptibility is complex even in individual fish and extrapolation from observed changes in immune response to disease susceptibility can be difficult. In the past there has been much unexplained variation among populations and individuals (e.g. Walters Plumb, 1980) and only recently have we started to understand the mechanisms underlying individual and population variability (Blanford et al, 2003 Lafferty Holt, 2003 MacKenzie et al, 2009). 

The biochemical and physiological effects of cortisol are snmmarised in Figure 12.10. Higher than normal concentrations of cortisol improve mood and reduce the activity of the immune system. Hence, they are routinely used to reduce chronic inflammation. There are, however, side-effects of these high levels increased levels of blood glucose, obesity and retention of water giving rise to moon face . 

Several explanations have been suggested, including a decrease in the number of immune cells, an increase in the level of stress hormones (especially cortisol, which depresses the immune system), and a decreased level of glucose and glutamine in the blood (Chapter 17). 

The adrenocorticosteroids have several important physiologic and pharmacologic functions. The glucocorticoids (cortisol, corticosterone) are primarily involved in the control of glucose metabolism and the body s ability to deal with stress. Glucocorticoids have other attributes, such as their ability to decrease inflammation and suppress the immune system. Mineralocorticoids, such as aldosterone, are involved in maintaining fluid and electrolyte balance in the body. 

The two principal groups of adrenal steroids are the glucocorticoids and mineralocorticoids. These hormones are synthesized from cholesterol within cells of the adrenal cortex. The primary glucocorticoid produced in humans is cortisol (hydrocortisone), and the primary mineralocorticoid is aldosterone. Glucocorticoids exert a number of effects such as regulation of glucose metabolism, attenuation of the inflammatory response, and suppression of the immune system. Mineralocorticoids are involved primarily in the control of fluid and electrolyte balance. 

Glucocorticoid The general class of steroid agents that affect glucose metabolism and are used pharmacologically to decrease inflammation and suppress the immune system. Principle examples include cortisol and corticosterone. 

Figure 18.2. Endocrine-immune inter-relationship in normal subject. The hypothalamic-pituitary-adrenal (HPA) axis is a feedback loop that includes the hypothalamus, the pituitary and the adrenal glands. The main hormones that activate the HPA axis are corticotrophin releasing factor (CRF), arginine vasopressin (AVP) and adrenocorticotrophic hormone (ACTH). The loop is completed by the negative feedback of cortisol on the hypothalamus and pituitary. The simultaneous release of cortisol into the circulation has a number of effects, including elevation of blood glucose for increased metabolic demand. Cortisol also negatively affects the immune system and prevents the release of immunotransmitters. Interference from other brain regions (e.g. hippocampus and amygdala) can also modify the HPA axis, as can neuropeptides and neurotransmitters.

The effect of stress on the endocrine and immune systems depends upon its duration and severity. Following acute stress, the rise in ACTH in response to the release of corticotrophin releasing factor (CRF) from the hypothalamus results in a rise in the synthesis and release of cortisol from the adrenals. The increase in the plasma cortisol concentration results in a temporary suppression of many aspects of cellular immunity. Due to the operation of an inhibitory feedback mechanism, stimulation of the central glucocorticoid receptors in the hypothalamus and pituitary causes a decrease in the further release of CRF, thereby decreasing the further... 

Figure 18.3. Endocrine-immune inter-relationship in depression. In depression, the hypothalamic-pituitary-adrenal (HPA) axis is up-regulated with a down-regulation of its negative feedback controls. Corticotrophin releasing factor (CRF) is hypersecreted from the hypothalamus and induces the release of adrenocortico-trophic hormone (ACTH) from the pituitary. ACTH interacts with receptors on adrenocortical cells and cortisol is released from the adrenal glands adrenal hypertrophy can also occur. Release of cortisol into the circulation has a number of effects, including elevation of blood glucose. The negative feedback of cortisol to the hypothalamus, pituitary and immune system is impaired. This leads to continual activation of the HPA axis and excess cortisol release. Cortisol receptors become desensitized leading to increased activity of the pro-inflammatory immune mediators and disturbances in neurotransmitter transmission.

Suppression of the immune system, because of long-term increase in the level of cortisol. 

The immune system plays a major role in pain. Under pain situations, IL-1 induces a decrease inthe level of CRF, cortisol, and p-endorphin (Bessler, et al., 1996 Parsadaniatz, et al., 1997). CRF alone releases p-endorphin. IL-1 alone has the similar effect—releasing P-endorphin. n-3 Fatty acids protected the rats from opiate side effects (Frances, et al., 1996, Hargreaves et al., 1990, Jones et al., 1999). IL-1, on the other hand, increases the level of PGE2 (Hori, et al., 1998) to increase pain sensation. 

As the major stress hormone, cortisol has many functions. For example, in trabecular bone, cortisol inhibits synthesis of new bone by osteoblasts and decreases absorption of Ca + in the G1 tract, leading to osteopenia. However, the two principal influences of cortisol are on metabolism and the immune system. 

But there are also long-term stresses that may damage the brain and the immune system over time. This happens when our brains remain on orange alert, when we feel helpless, perhaps when we have been ill and when worry and grief consume us. When that happens, we release another set of hormones, the best studied of which is called cortisol. We release this hormone from the cortical (outer shell portion) of our adrenal glands and pump it into our bloodstream. 

There are practical reasons to focus on those things you can control. Sources of chronic distress can lead to chronically elevated levels of stress hormones such as cortisol that suppress your immune system. In turn, you become more vulnerable to getting sick with infectious diseases or even with certain kinds of cancer. Ongoing fear and anxiety can contribute to a learned-helplessness mindset. That by itself can induce depression. And depression can further impair cognition. 

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