5-HT and the immune system

Ahern, Gerard P.

doi:10.1016/j.coph.2011.02.004

Cited by 205 publications

(170 citation statements)

References 23 publications

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“…They may correspond to neutrophils involved in the very early stages following peripheral nerve injury [14,48], with a decrease in infiltration by these cells attenuating mechanical allodynia [25]. Other immune cells express the receptor [1], including T lymphocytes [56]. However, their involvement is unlikely, because Tlymphocyte infiltration occurs three days after the nerve lesion and peaks at day 21 [5] well after the observed peak in 5-HT 2B R mRNA levels observed in this study (day 2).…”

Section: Discussionmentioning

confidence: 68%

“…In the spinal cord, 5-HT acts through bulbospinal descending projections [30,38,54], whereas, in the periphery, it sensitizes nociceptors following both inflammation and nerve injury [53]. By contrast, the role of 5-HT in the immune mechanisms associated with neuropathic pain has never been addressed, despite the abundance of data implicating 5-HT in immune functions [1,9,21,33,44]. Interestingly, one study [61] has already described an antinociceptive effect of dexfenfluramine, a 5-HT releaser that is metabolized in norfenfluramine, a preferential 5-HT 2B receptor agonist [23].…”

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confidence: 97%

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Antinociceptive effect of peripheral serotonin 5-HT2B receptor activation on neuropathic pain

Urtikova

Berson

Steenwinckel

et al. 2012

Pain

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-nociceptive effect of peripheral serotonin 5-HT2B receptor activation on neuropathic pain.. PAIN, Elsevier, 2012, 153 (6), pp.1320-31. <10.1016/j.pain.2012.03.024>. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 receptor. CCI resulted in a biphasic upregulation of 5-HT 2B receptor expression in lumbar dorsal root ganglia, consisting of a transient early increase (23-fold), two days after surgery, before the development of neuropathic pain, followed by a steady, five times increase, levels remaining constant thereafter until the pain disappeared. 5-HT 2B receptors were immmunolocalized mostly on primary sensory neurons and infiltrating macrophages. Intrathecal injection of RS127445, a selective 5-HT 2B receptor antagonist, enhanced mechanical and cold allodynia. A single application of BW732C86, a 5-HT 2B agonist, to the sciatic nerve immediately after ligature completely prevented mechanical allodynia and significantly decreased cold allodynia. This effect was dose-dependent and reversed by a 5-HT 2B antagonist. We also observed a marked decrease in macrophage infiltration of the sciatic nerve, neuropathic pain markers and cytokine induction. Our data reveal the relationships between serotonin, the immune system and neuropathic pain, and demonstrate a critical role of 5-HT 2Breceptors in blood-derived macrophages.

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Section: Discussionmentioning

confidence: 68%

mentioning

confidence: 97%

Antinociceptive effect of peripheral serotonin 5-HT2B receptor activation on neuropathic pain

Urtikova

Berson

Steenwinckel

et al. 2012

Pain

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“…First, serotonergenic receptors have been identified on various immune cells such as type B and T lymphocytes, monocytes, macrophage, and dentritic cells. 44,45 Second, Leoń-Ponte and colleagues proposed that Tph1-derived 5-HT synthesized by T cells may act as an autocrine factor and demonstrated a fundamental role for 5-HT as an intrinsic cofactor in T-cell activation and function. 46 To address the role of 5-HT in immune activation and regulation of gut inflammation, Ghia et al studied Tph1 KO mice and hypothesized that 5-HT activates and promotes survival of immune cells.…”

Section: ■ Tph1-derived Serotonin In the Gut: What Does It Really Do?mentioning

confidence: 99%

Life without Peripheral Serotonin: Insights from Tryptophan Hydroxylase 1 Knockout Mice Reveal the Existence of Paracrine/Autocrine Serotonergic Networks

Amireault

Sibon

Côté

2012

ACS Chem. Neurosci.

138

113

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Since its identification, 75 years ago, the monoamine serotonin (5-HT) has attracted considerable attention toward its role as a neurotransmitter in the central nervous system. Yet, increasing evidence, from a growing number of research groups, substantiates the fact that 5-HT regulates important nonneuronal functions. Peripheral 5-HT, synthesized by the enzyme tryptophan hydroxyase (Tph) in intestinal cells, was assumed to be distributed throughout the entire body by blood platelets and to behave as a pleiotropic hormone. A decade ago, generation of a mouse model devoid of peripheral 5-HT lead to the discovery of a second isoform of the enzyme Tph and also suggested that 5-HT might act as a local regulator in various organs. The objective of this review is to highlight the newly discovered functions played by the monoamine using the Tph1 KO murine model and to outline current findings that led to the discovery of complete serotonergic systems in unexpected organs. Within an organ, both the presence of local Tph enzymatic activity and serotonergic components are of particular importance as they support the view that 5-HT meets the criteria to be qualified as a monoamine with a paracrine/autocrine function.

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“…By acting as ambient serotonin level sensors, macrophages could modulate genotype expression patterns in macrophages: activation of 5HT 7 receptors in macrophages has been noted to induce polarization towards the antiinflammatory M2 phenotype [33,34] . Inhibition of TNFα and IL-6 release, as well as promotion of IL-10 synthesis, are prominent among the antiinflammatory features of M2 macrophages [33,35,36] . Nevertheless, these antiinflammatory effects have been speculated to occur only at doses greater than the usual therapeutic range [37] , and SSRIs may rather be proinflammatory at lower doses, especially with prolonged use [38] .…”

Section: Ssri-associated Cardiometabolic Risk: Molecular Pathwaysmentioning

confidence: 99%

Metabolic risk in depression and treatment with selective serotonin reuptake inhibitors: are the metabolic syndrome and an increase in cardiovascular risk unavoidable?

Chávez-Castillo¹,

Ortega²,

Nava³

et al. 2018

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Depression is one of the most common psychiatric disorders, and has become an epidemic in modern medical practice; notorious for frequently co-occurring with multiple comorbidities, especially cardiovascular disease (CVD), type 2 diabetes mellitus (DM2), and its various risk factors comprised in the metabolic syndrome (MS). Selective serotonin reuptake inhibitors (SSRIs) are the most widely used class of psychotropic drugs in this and many other clinical scenarios; yet their impact on cardiometabolic health has not been elucidated. The objective of this review was to summarize current views on the pharmacology of SSRIs and cardiometabolic risk, as well as available epidemiological evidence regarding its clinical significance. SSRIs appear to intervene in cardiometabolic physiology fundamentally by modulating chronic inflammation, a key pathophysiologic phenomenon in MS, DM2 and CVD. However, the dosing necessary to achieve a beneficial impact in this regard, as well as their clinical correlations, remain controversial. Each SSRI displays a particular profile regarding each of the components of the MS: weight gain seems to be the most common effect of SSRIs, more frequent with paroxetine, followed by citalopram and escitalopram. As a drug class, SSRIs also appear to promote hypercholesterolemia rather uniformly, while fluoxetine and citalopram appear to particularly increase triacylglyceride levels. In contrast, fluvoxamine and paroxetine seem to have the greatest impact on dysglycemia. Lastly, most SSRIs appear to be innocuous or even beneficial regarding blood pressure and high-density lipoprotein cholesterol. Nevertheless, many of these effects may vary significantly upon specific clinical circumstances, especially timing. This topic remains rather unexplored in clinical psychopharmacology, and further, larger-scale epidemiological studies are needed in order to offer improved care in this field.

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5-HT and the immune system

Cited by 205 publications

References 23 publications

Antinociceptive effect of peripheral serotonin 5-HT2B receptor activation on neuropathic pain

Antinociceptive effect of peripheral serotonin 5-HT2B receptor activation on neuropathic pain

Life without Peripheral Serotonin: Insights from Tryptophan Hydroxylase 1 Knockout Mice Reveal the Existence of Paracrine/Autocrine Serotonergic Networks

Metabolic risk in depression and treatment with selective serotonin reuptake inhibitors: are the metabolic syndrome and an increase in cardiovascular risk unavoidable?

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