Abstract
Changes of the tumor necrosis factor-alpha (TNF-α) system have been shown to be involved in the development of psychiatric disorders and are additionally associated with changes in body weight as well as endocrine and metabolic changes in psychiatric patients. TNF-α might, for example, contribute to the pathogenesis of depression by an activation of the hypothalamo-pituitary-adrenocortical (HPA) axis, an activation of neuronal serotonin transporters and the stimulation of the indoleamine 2,3-dioxygenase which leads to tryptophan depletion. On the other hand, during an acute depressive episode, an elevated HPA axis activity may suppress TNF-α system activity, while after remission, when HPA axis activity has normalized the suppression of the TNF-α system has been shown not to be apparent any more.In narcoleptic patients, soluble TNF receptor (sTNF-R) p75 plasma levels have been shown to be elevated, suggesting a functional role of the TNF-α system in the development of this disorder.Additionally, psychotropic drugs influence the TNF-α system as well as the secretion and the effect of hormones which counteract or interact with the TNF-α system such as the intestinal hormone ghrelin. However, only preliminary studies with restricted sample sizes exist on these issues, and many open questions remain.
Highlights
The brain and the immune system are the two major adaptive systems of the body
More and more support for the hypothesis is found that the tumor necrosis factor (TNF)- producing macrophages play an important role in neurodevelopment and in the pathophysiology of various neuropsychiatric conditions [19]
The central nervous system affects the immune system mainly through the neuroendocrine outflow via the pituitary, and through direct neuronal influences via the sympathetic, parasympathetic, peptidergic and sensory innervation of peripheral tissues. Certain cytokines such as interleukin (IL)-1, IL-6 and TNF- released during an immune response and other processes the immune system is involved in modulate brain activity
Summary
The brain and the immune system are the two major adaptive systems of the body. Both influence and regulate each other. As increased pro-inflammatory cytokine levels are known to be associated with cardiovascular disease [25, 41, 81], silent brain infarctions [39], and a worse prognosis after stroke [102], Park et al concluded that the positive associations of obesity and visceral adiposity with elevated cytokine levels suggest the importance of reducing obesity and visceral adiposity to prevent elevations in cytokine levels and associated diseases [65] Cytokines such as TNF- link the non-specific immune system to the hypothalamo-pituitary-adrenocortical (HPA) axis: inflammatory cytokines — such as TNF- and its soluble receptors p55 and p75 — released during infection and inflammation activate the HPA system at the hypothalamic, pituitary, and adrenal level resulting in the release of cortisol as the most important negative feedback signal to prevent an overshoot of the ongoing host defense [42, 89, 96]; glucocorticoids, in turn, suppress the production of pro-inflammatory cytokines. Appetite loss and fever lead to lipolysis, lipid mobilization and a reduction of the fatty tissue
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