Immunomodulatory Effects Mediated by Serotonin

Abstract

Serotonin (5-HT) induces concentration-dependent metabolic effects in diverse cell types, including neurons, entherochromaffin cells, adipocytes, pancreatic beta-cells, fibroblasts, smooth muscle cells, epithelial cells, and leukocytes. Three classes of genes regulating 5-HT function are constitutively expressed or induced in these cells: (a) membrane proteins that regulate the response to 5-HT, such as SERT, 5HTR-GPCR, and the 5HT3-ion channels; (b) downstream signaling transduction proteins; and (c) enzymes controlling 5-HT metabolism, such as IDO and MAO, which can generate biologically active catabolites, including melatonin, kynurenines, and kynurenamines. This review covers the clinical and experimental mechanisms involved in 5-HT-induced immunomodulation. These mechanisms are cell-specific and depend on the expression of serotonergic components in immune cells. Consequently, 5-HT can modulate several immunological events, such as chemotaxis, leukocyte activation, proliferation, cytokine secretion, anergy, and apoptosis. The effects of 5-HT on immune cells may be relevant in the clinical outcome of pathologies with an inflammatory component. Major depression, fibromyalgia, Alzheimer disease, psoriasis, arthritis, allergies, and asthma are all associated with changes in the serotonergic system associated with leukocytes. Thus, pharmacological regulation of the serotonergic system may modulate immune function and provide therapeutic alternatives for these diseases.

Synergistic Effect of Galantamine Carried on a Novel Nano-Drug Delivery System on Induced Lung Disorders in Alzheimer’s Disease

“…[42,43] It is one of the most important neurotransmitters in the central nervous system (CNS) regulating multiple physiological functions such as body temperature, appetite, sleep, mood and pain. [44] Several studies reported that pathological change in 5-HT level have been associated with AD, anxiety and Depression. [45,46] The decrease in the level of tissue 5-HT may be attributed to amyloid depositions in the projection sites of serotonergic neurons lead to the degeneration of 5-HT axons followed by the degeneration of the corresponding neuronal cell bodies.…”

Serotonin in Neurological Diseases

“…The T102C polymorphism in HTR2A gene encoding 5-HT2A is also postulated to be a risk factor for FM [38]. As 5-HT2 and 5-HT3 are involved in pain perception, the treatment with 5-HT3 antagonist or inhibition of 5-HT reuptake is effective in FM patients [39]. The SSRI administration is necessary as depression is a common disorder among FM patients and it is present in up to 80% of individuals [34].…”

Undeniable Neuroimmunology

“…The cells of the immune system possess all the components of the serotonergic system, having the necessary machinery to not only be sensitive to serotonin, but also to produce and catabolize this amine [31]. Despite of attending to "molecular prerequisites", the action of the serotonin on the modulation of the immune response is still underexplored.…”

“…Despite of attending to "molecular prerequisites", the action of the serotonin on the modulation of the immune response is still underexplored. What it's known is that it can induce to changes in the profile of the leukocyte secreted cytokines [31]. Besides, some studies suggest the existence of a complex cross-communication mechanism between the signaling triggered by 5-HT receptors and the signaling induced by molecular pattern recognition receptors [32].…”