Specific Serotonin Reuptake Inhibitor-Induced Decreases in Lymphocyte Activity Require Endogenous Serotonin Release

Pellegrino, Trisha C.; Bayer, Barbara

doi:10.1159/000054278

Cited by 39 publications

(29 citation statements)

References 49 publications

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“…However, others found that in rats, elevations in extracellular 5-HT following reuptake inhibition by fluoxetine played an essential role in decreasing mitogen-induced lymphocyte proliferation [43]. …”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effect of Sertraline in a Rat Model of Rheumatoid Arthritis

Baharav

Bar²,

Taler³

et al. 2012

Neuroimmunomodulation

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Objective: Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) modulate immune system functionality. SSRIs are the preferred treatment for major depressive disorder (MDD). A high rate of MDD is observed in rheumatoid arthritis (RA) patients. The aim of this study was to evaluate immunological effects of SSRIs in a rat model of RA. Methods: Adjuvant arthritis was induced in 8-week-old Lewis rats; in the first set of experiments following the induction, 15.3 or 30.6 mg/kg of sertraline was daily injected into the ankle joint of the left rear leg. Clinical disease activity was evaluated and the findings compared with the 3 untreated legs and with control groups given methotrexate (MTX) or vehicle only at the same site. In a second set of experiments, the effect of 5, 25 and 50 mg/kg daily oral sertraline was evaluated in the same rat model. Splenocyte viability and inflammatory mediators were evaluated. Results: The sertraline-treated rats showed a significant reduction in clinical arthritis compared to controls, at all doses given, accompanied by a significant increase in interleukin 10 and a decrease in tumor necrosis factor-α levels and cycloxygenase-2 production, without lymphotoxicity. There was no significant difference from MTX, the first-line treatment for RA patients. Oral sertraline had a significant anti-inflammatory effect at all doses. There was no treatment × time effect. Conclusion: The beneficial effects of sertraline in this rat model of arthritis have clinical implications for its use in humans. Large-scale clinical efficacy trials are needed.

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Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effect of Sertraline in a Rat Model of Rheumatoid Arthritis

Baharav

Bar²,

Taler³

et al. 2012

Neuroimmunomodulation

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“…Further support was given by the effect of 5-HT reuptake inhibitors, which decreased cell proliferation. Moreover, endogenous 5-HT release is required for observing decrease in lymphocyte activity by 5-HT reuptake blockers [55].…”

Section: Discussionmentioning

confidence: 99%

5-HT<sub>1A </sub>and β-Adrenergic Receptors Regulate Proliferation of Rat Blood Lymphocytes

Sempere¹,

Urbina²,

Lima³

2004

Neuroimmunomodulation

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Lymphocytes possess serotonin 5-HT_1A and β-adrenergic receptors, which have been related to cell proliferation. In the present report, lymphocytes of rat blood were isolated by Ficoll-Hypaque gradients and differential adhesion to plastic. They were cultured in RPMI medium for 72 h in the presence of the mitogens lipopolysaccharide concanavalin A and anti-CD3 antibody. The latter two stimulated the proliferation of lymphocytes, but not the first. Serotonin (0.1–100 µM) was added alone or in the presence of suboptimal concentrations of concanavalin A (2 µg/ml) or anti-CD3 antibody (0.4 µg/ml). The 5-HT_1A receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin and buspirone (0.1–100 µM) were also tested in the cultures. Serotonin, 8-hydroxy-2-(di-n-propylamino)tetralin and buspirone neither had any effect by themselves, nor modified the proliferation induced by the mitogens. Noradrenaline (25–1,000 µM) and the β-adrenergic receptor agonist, isoproterenol (5–100 µM), produced a reduction of the activation induced by concanavalin A or anti-CD3 antibody in a dose-dependent manner. Increasing serotonin concentrations reduced the inhibitory effect of noradrenaline (300 µM). Variable concentrations of 8-hydroxy-2-(di-n-propylamino)tetralin or buspirone also reduced the inhibition produced by isoproterenol (100 µM). The antagonist of 5-HT_1A receptors, WAY-100,478 (0.1–100 µM), inhibited concanavalin A- or anti-CD3 antibody-induced proliferation. Serotonin (0.1–100 µM) impaired the inhibitory effect of the 5-HT_1A antagonist (10 µM). The inhibitor of tryptophan hydroxylase, p-chlorophenylalanine (50–1,000 µM), decreased the stimulatory effect of concanavalin A, serotonin (0.5–100 µM) and 8-hydroxy-2-(di-n-propylamino)tetralin (1–100 µM) reverted the effect of p-chlorophenylalanine (1,000 µM). The serotonin reuptake blockers zimelidine, imipramine and clomipramine decreased concanavalin A-induced proliferation. The concentrations of serotonin and noradrenaline increased in lymphocytes cultured in the presence of concanavalin A, probably as a mechanism for modifying the final effect on proliferation. The present results indicate that 5-HT_1A receptors play a stimulatory role on rat blood lymphocytes, and they interact in a parallel and opposite manner with β-adrenergic receptors. Furthermore, endogenous serotonin is relevant in displaying its stimulatory effect.

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“…Acute treatment with SSRIs decreases lymphocyte proliferation. It has been proposed that such effect results from elevations in extracellular 5-HT due to inhibition of its uptake as a consequence of such treatment [28].…”

Section: -Ht Transportermentioning

confidence: 99%

Serotonin as a Modulator of Immune Function: An Overview

Cloëz‐Tayarani

2006

CIR

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The CNS and immune system interact in a reciprocal manner through a wide variety of common mediators including neurotransmitters and cytokines. Among the former, serotonin (5-Hydroxytryptamine = 5-HT) plays a major role in the control of neuronal activity. It may also control the level of cytokines and lymphocyte proliferation. 5-HT is synthesized and released in the circulation by enterochromaffin cells from gastric and intestinal mucosa. Under inflammatory conditions such as thrombosis and ischemia, the activated platelets release 5-HT at the site of inflammation and lead to an increase in its local concentration. In addition to its possible interaction with blood cells, 5-HT may also interact with the inflamed tissue macrophages through its various receptors. Accordingly, 5-HT transporters and 5-HT receptor subtypes have been characterized in different blood cells. This review provides an overview of reported data on the regulatory role of 5-HT on the activity of peripheral blood cells. Such role includes both immunostimulatory and immunoinhibitory effects based on 5-HT concentration and its cellular target. In the light of recent data, this review also speculates on the intracellular processes (i.e. MAP kinases), which are activated by 5-HT suggesting neuromodulatory function.

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Specific Serotonin Reuptake Inhibitor-Induced Decreases in Lymphocyte Activity Require Endogenous Serotonin Release

Cited by 39 publications

References 49 publications

Immunomodulatory Effect of Sertraline in a Rat Model of Rheumatoid Arthritis

Immunomodulatory Effect of Sertraline in a Rat Model of Rheumatoid Arthritis

5-HT<sub>1A </sub>and β-Adrenergic Receptors Regulate Proliferation of Rat Blood Lymphocytes

Serotonin as a Modulator of Immune Function: An Overview

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