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Various hormones and factors

Figure 18.1. Summary of the pathways postulated to be involved in the interaction between the nervous and immune systems.

Various hormones and factors

Figure 18.1. Summary of the pathways postulated to be involved in the interaction between the nervous and immune systems.

the sympathetic system is responsible for the catecholamine secretion. It is now apparent that ACTH secretion can also be increased by thymic peptides (such as thymopoietin), while interleukin-1 (IL-alpha), a product of macrophage activity, has been shown to enhance ACTH secretion.

Such events show how the immune, endocrine and central nervous systems are integrated in their responses to any form of stress. It is well established that physical or psychosocial stress causes increased secretions of prolactin, growth hormones, thyroid, and gonadal hormones, in addition to ACTH. Endogenous opioids are secreted under such conditions and function as immunomodulators, while also elevating the pain threshold. Receptors for such hormones exist on immunocompetent cells, along with receptors for catecholamines, serotonin and acetylcholine.

In addition to the regulatory effects of the nervous system on the immune system, there is now convincing evidence that the immune system can influence brain function. Thus changes in the activity of specific nuclei in the hypothalamus of the rat have been described following the formation of antibodies to specific antigen challenges. Alterations in electrical activity appear to be linked to specific decreases in noradrenaline concentrations in these nuclei. Changes in the activity of the serotonergic neurons in the hippocampus also occur shortly after the occurrence of the immune response. These findings illustrate how the immune system, presumably via the release of immunoregulatory peptides (also called immunotransmitters) such as interleukins from macrophages, can influence the activity of the cortex cortex

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Cortisol

Figure 18.2. Endocrine-immune inter-relationship in normal subject. The hypotha-lamic-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.

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Figure 18.2. Endocrine-immune inter-relationship in normal subject. The hypotha-lamic-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.

hypothalamic-pituitary axis and also higher centres of the brain (such as the hippocampus), which are involved in short-term memory processing. The triad of inter-relationships between the brain, endocrine and immune systems is illustrated in Figures 18.2, 18.3, 18.4 and 18.5.

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 des^nsitisation of Cortisol receptors des^nsitisation of Cortisol receptors

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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.

synthesis and release of cortisol. Arginine vasopressin (AVP) also plays a role in activating the release of ACTH from the anterior pituitary gland.

Following chronic stress, however, the regulatory feedback inhibitory mechanism is dysfunctional due to the desensitization of the central and peripheral glucocorticoid receptors. Thus cortisol continues to be secreted primarily due to the activation of the hypothalamic-pituitary axis by AVP and the elevated pro-inflammatory cytokines such as interleukin-1. Due to the desensitization of the glucocorticoid receptors on the immune cells and in the brain, and a lack of inhibition by glucocorticoids of central macrophage activity (the astrocytes and glial cells), glucocorticoids continue to be secreted.

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Figure 18.4. Endocrine-immune inter-relationship following acute stress. In response to stress, corticotrophin releasing factor (CRF) and arginine vasopressin (AVP) are secreted from the hypothalamus causing 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. Release of cortisol into the circulation has a number of effects, including elevation of blood glucose. The negative feedback of cortisol on the hypothalamus, pituitary and immune system remains unaffected in acute stress - the release of CRF, AVP and immunotransmitters is still inhibited, preventing the continual activation of the

HPA axis.

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Figure 18.4. Endocrine-immune inter-relationship following acute stress. In response to stress, corticotrophin releasing factor (CRF) and arginine vasopressin (AVP) are secreted from the hypothalamus causing 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. Release of cortisol into the circulation has a number of effects, including elevation of blood glucose. The negative feedback of cortisol on the hypothalamus, pituitary and immune system remains unaffected in acute stress - the release of CRF, AVP and immunotransmitters is still inhibited, preventing the continual activation of the

HPA axis.

Immune system in affective disorders

Susceptibility to bacterial and viral infections, and to the establishment of tumours, is reported to arise more frequently in those who are depressed than in those who are not. An analysis of the immune systems of those suffering the severe psychological stress of bereavement has shown that the activity of those immune cells that are fundamentally involved in the host defence against infections (e.g. NKCs and T-lymphocytes) is dramatically reduced. Such an effect can occur following chronic and subchronic stress.

The past 20 years have witnessed a broad interest in the role of the hypothalamic-pituitary-adrenal axis in the psychobiology of affective disorders. In depressed patients, increases in serum cortisol are frequently reported in addition to disruptions of circadian patterns of cortisol secretion hippocampus -I- ar el ease ol A.VP

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