Selective serotonin reuptake inhibitors as a novel class of immunosuppressants

Gobin, Veerle; Steendam, Katleen Van; Denys, Damiaan; Deforce, Dieter

doi:10.1016/j.intimp.2014.02.030

Cited by 77 publications

(71 citation statements)

References 76 publications

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“…The mechanisms underlying the effects of SSRIs on the immune system under normal and pathological situations remain to be clarified (Gobin et al, 2014). Taler et al (2008) and Gobin et al (2014) suggested that the immunomodulatory effect of SSRIs would be related to their pro-apoptotic activity, and to their action on lymphocyte proliferation and to cytokine secretion. This may have been the case in our work as a consequence of normalizing the altered neuroendocrine function in prenatally stressed animals.…”

Section: Discussionmentioning

confidence: 99%

The effects of sertraline administration from adolescence to adulthood on physiological and emotional development in prenatally stressed rats of both sexes

Pereira-Figueiredo

Sancho

Carro

et al. 2014

Front. Behav. Neurosci.

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Sertraline (SERT) is a clinically effective Selective Serotonin Reuptake Inhibitor (SSRI) known to increase and stabilize serotonin levels. This neurotransmitter plays an important role in adolescent brain development in both rodents and humans, and its dysregulation has been correlated with deficits in behavior and emotional regulation. Since prenatal stress may disturb serotoninergic homeostasis, the aim of this study was to examine the long-lasting effects of exposure to SERT throughout adolescence on behavioral and physiological developmental parameters in prenatally stressed Wistar rats. SERT was administered (5 mg/kg/day p.o.) from the age of 1–3 months to half of the progeny, of both sexes, of gestating dams stressed by use of a restraint (PS) or not stressed. Our data reveal that long-term SERT treatment slightly reduced weight gain in both sexes, but reversed the developmental disturbed “catch-up” growth found in PS females. Neither prenatal stress nor SERT treatment induced remarkable alterations in behavior and had no effects on mean startle reflex values. However, a sex-dependent effects of PS was found: in males the PS paradigm slightly increased anxiety-like behavior in the open field, while in females, it impaired startle habituation. In both cases, SERT treatment reversed the phenomena. Additionally, the PS animals exhibited a disturbed leukocyte profile in both sexes, which was reversed by SERT. The present findings are evidence that continuous SERT administration from adolescence through adulthood is safe in rodents and lessens the impact of prenatal stress in rats.

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Section: Discussionmentioning

confidence: 99%

The effects of sertraline administration from adolescence to adulthood on physiological and emotional development in prenatally stressed rats of both sexes

Pereira-Figueiredo

Sancho

Carro

et al. 2014

Front. Behav. Neurosci.

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“…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] . This is consistent with evidence from Kubera et al [27] , who found physiological levels of intracellular serotonin tend to promote TNFα and IL-6 synthesis in macrophages, whereas supraphysiological levels of extracellular serotonin were linked with downregulation of serotonin receptors serotonin receptors and with decreased release of with decreased release of proinflammatory cytokines.…”

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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“…In the spleen, 5-HT increases monocyte differentiation into dendritic cells and early naive T-cell activation via the 5-HT 2A receptor [38,39]. Furthermore, it also has been shown that lymphocytic cytokine levels in mice are reduced after treatment with SSRI [40]. In a mouse model of viral hepatitis, the release of 5-HT by platelets was responsible for tissues damage caused by CD8 (+) T-cells, microcirculatory events, and reduced clearance of infiltrated viruses [33].…”

Section: Serotonin -A Chemical Messenger Between All Types Of Living mentioning

confidence: 99%

Immuno-Thrombotic Effects of Platelet Serotonin

Mammadova‐Bach¹,

Mauler²,

Braun³

et al. 2017

Serotonin - A Chemical Messenger Between All Types of Living Cells

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Platelets transport and store serotonin at a high concentration in dense granules and release it upon activation. Abnormal serotonin concentrations in the blood plasma or increased platelet serotonin release promote the development of thrombosis, sepsis, allergic asthma, myocardial infarction, and stroke. Consequently, experimental data suggest possible benefits of serotonin receptor blockade or inhibition of platelet serotonin uptake in the indicated human diseases. Here, we highlight the current state of basic biological research regarding the role of platelet serotonin in normal and pathophysiological conditions focusing on thrombotic and inflammatory diseases. We also describe the possible clinical applicability of targeting thrombo-immune-modulatory effects of platelet serotonin to treat common health problems.

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Selective serotonin reuptake inhibitors as a novel class of immunosuppressants

Cited by 77 publications

References 76 publications

The effects of sertraline administration from adolescence to adulthood on physiological and emotional development in prenatally stressed rats of both sexes

The effects of sertraline administration from adolescence to adulthood on physiological and emotional development in prenatally stressed rats of both sexes

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

Immuno-Thrombotic Effects of Platelet Serotonin

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