Serotonin inhibition of tumor necrosis factor-α synthesis by human monocytes

Arzt, Eduardo; Costas, Mónica Alejandra; Finkielman, Samuel; Nahmod, Víctor E.

doi:10.1016/0024-3205(91)90612-f

Cited by 75 publications

(37 citation statements)

References 20 publications

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“…Results here showed that fluoxetine pre-treatment significantly prevented increases in TNF levels in both models; this would support an antiinflammatory effect of fluoxetine noted in previous studies (Abdel-Salam et al 2003;Mozaffari et al 2011). This ability of fluoxetine to inhibit TNF formation/ release may be attributed to its impact on serotonin, as serotonin can inhibit monocyte TNF synthesis (Arzt et al 1991) and up-regulate expression of COX isoforms; as noted earlier, PGE 2 can also inhibit production of TNF (Menard et al 2007). Fluoxetine also significantly inhibited INDO-and ethanol-induced increases in MPO levels here; this outcome was in agreement with a previous study that demonstrated an inhibitory effect of fluoxetine on MPO levels in irritable bowel syndrome (Kato et al 1998).…”

Section: Discussionmentioning

confidence: 89%

Serotonin and histamine mediate gastroprotective effect of fluoxetine against experimentally-induced ulcers in rats

Sokar

Elsayad

Ali

2016

Journal of Immunotoxicology

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Research in the treatment of gastric ulcer has involved the investigation of new alternatives, such as anti-depressant drugs. The present study was designed to investigate the gastroprotective effects of fluoxetine against indomethacin and alcohol induced gastric ulcers in rats and the potential mechanisms of that effect. Fluoxetine (20 mg/kg) was administered IP for 14 days. For comparative purposes, other rats were treated with ranitidine (30 mg/kg). Thereafter, after 24 h of fasting, INDO (100 mg/kg) or absolute alcohol (5 ml/kg) was administered to all rats (saline was administered to naïve controls) and rats in each group were sacrificed 5 h (for INDO rats) or 1 h (for alcohol rats) later. Macroscopic examination revealed that both fluoxetine and ranitidine decreased ulcer scores in variable ratios, which was supported by microscopic histopathological examination. Biochemical analysis of fluoxetine-or ranitidine-pre-treated host tissues demonstrated reductions in tumor necrosis factor (TNF)-and myeloperoxidase (MPO) levels and concomitant increases in gastric pH, nitric oxide (NO) and reduced glutathione (GSH) contents. Fluoxetine, more than ranitidine, also resulted in serotonin and histamine levels nearest to control values. Moreover, immuno-histochemical analysis showed that fluoxetine markedly enhanced expression of cyclooxygenases COX-1 and COX-2 in both models; in comparison, ranitidine did not affect COX-1 expression in either ulcer model but caused moderate increases in COX-2 expression in INDOinduced hosts and high expression in alcohol-induced hosts. The results here indicated fluoxetine exhibited better gastroprotective effects than ranitidine and this could be due to anti-secretory, anti-oxidant, anti-inflammatory and anti-histaminic effects of the drug, as well as a stabilization of gastric serotonin levels. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 89%

Serotonin and histamine mediate gastroprotective effect of fluoxetine against experimentally-induced ulcers in rats

Sokar

Elsayad

Ali

2016

Journal of Immunotoxicology

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“…In peripheral blood, serotonin is released from platelets and lymphocytes/monocytes following stimulation by LPS and IFN-g (15), and it modulates cytokine production by myeloid cells (16). Physiologic concentrations of 5HT suppress IFN-g-induced MHC class II expression and phagocytosis in murine macrophages (17,18) and inhibit the LPS-induced IL-1b, IL-6, IL-8, IL-12p40, and TNF-a production by human monocytes and PBMCs (19)(20)(21). In human alveolar macrophages, serotonin inhibits IL-12 and TNF-a release, but it increases IL-10, NO, and PGE 2 production via 5HT 2 receptors (22).…”

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confidence: 99%

Serotonin Skews Human Macrophage Polarization through HTR2B and HTR7

Casas-Engel

Domínguez-Soto

Sierra‐Filardi

et al. 2013

The Journal of Immunology

177

126

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Besides its role as a neurotransmitter, serotonin (5-hydroxytryptamine, 5HT) regulates inflammation and tissue repair via a set of receptors (5HT1–7) whose pattern of expression varies among cell lineages. Considering the importance of macrophage polarization plasticity for inflammatory responses and tissue repair, we evaluated whether 5HT modulates human macrophage polarization. 5HT inhibited the LPS-induced release of proinflammatory cytokines without affecting IL-10 production, upregulated the expression of M2 polarization–associated genes (SERPINB2, THBS1, STAB1, COL23A1), and reduced the expression of M1-associated genes (INHBA, CCR2, MMP12, SERPINE1, CD1B, ALDH1A2). Whereas only 5HT7 mediated the inhibitory action of 5HT on the release of proinflammatory cytokines, both 5HT2B and 5HT7 receptors mediated the pro-M2 skewing effect of 5HT. In fact, blockade of both receptors during in vitro monocyte-to-macrophage differentiation preferentially modulated the acquisition of M2 polarization markers. 5HT2B was found to be preferentially expressed by anti-inflammatory M2(M-CSF) macrophages and was detected in vivo in liver Kupffer cells and in tumor-associated macrophages. Therefore, 5HT modulates macrophage polarization and contributes to the maintenance of an anti-inflammatory state via 5HT2B and 5HT7, whose identification as functionally relevant markers for anti-inflammatory/homeostatic human M2 macrophages suggests their potential therapeutic value in inflammatory pathologies.

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“…5-HT2A/C antagonists modulate IFN␥-induced phagocytosis by murine macrophages (Sternberg et al 1987). Arzt et al (1991) reported that 5-HT inhibits-in a concentration dependent way-the LPS-induced production of tumor necrosis factor by human macrophages, and that this effect was blocked by the 5-HT2 receptor antagonist, ketanserin. On the other hand, 5-HT2A/C receptor antagonists were not able to inhibit PHA-stimulated proliferation of T cells (Aune et al 1994;Nordlind et al 1992).…”

Section: Discussionmentioning

confidence: 99%

“…Arzt et al (1991) showed that 5-HT inhibits, in a concentration-dependent way, the LPS-induced production of tumor necrosis factor by human macrophages. This effect was blocked by the 5-HT2 receptor antagonist, ketanserin.…”

mentioning

confidence: 99%

Effects of Serotonin and Serotonergic Agonists and Antagonists on the Production of Interferon-γ and Interleukin-10

Kubera¹,

Kenis²,

Bosmans³

et al. 2000

Neuropsychopharmacology

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(5-HT) is a neurotransmitter and an immune modulator. In vitro , antidepressants with a serotonergic mode of action have, at concentrations within the therapeutical range, negative immunoregulatory effects, i.e., they increase the production rate of interleukin-10 (IL-10), a negative immunoregulatory cytokine. We have hypothesized that part of these effects may be explained by the serotonergic activities of antidepressants on immunocytes. This study was carried out to examine the effects of 5-HT, p-chlorophenylalanine (PCPA), a 5-HT depleting agent, flesinoxan , and ritanserin (a 5-HT2A/ 2C antagonist) on the production rate of interferon-␥ (IFN ␥ ), a proinflammatory cytokine, and IL-10 by whole blood stimulated with polyclonal activators. The IFN ␥ /IL-10 production ratio was computed, since this ratio reflects the pro-versus anti-inflammatory capacity of cultured whole blood. We found that: 1) 5-HT, 150 ng/mL, 1.5 g/ mL, and 15 g/mL significantly decreased the IFN ␥ /IL-10 ratio; 2) PCPA (5 M) significantly suppressed the production of 3) Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter, a vasoactive amine released by platelets at sites of inflammation and an immune modulator (Roszman et al. 1985;Mossner and Lesch 1998;Kubera and Maes 1999). In humans, 5-HT is produced, outside the central nervous system, by enterochromaffin cells and it is stored in circulating platelets and to a lesser extent in monocytes and lymphocytes (Essmann 1978). 5-HT is released from platelets and lymphocytes/monocytes following stimulation by platelet activating factors or lectins/interferon-␥ (IFN ␥ ), respectively (Finocchiaro et al. 1988 (Cohen et al. 1985;Felten et al. 1991). Pharmacological and molecular analyses have confirmed the presence of 5HT1A and 5HT2A/C receptors on activated human immunocytes and specific 5-HT transporter sites on macrophages/ lymphocytes (Aune et al. 1994).The effect of 5-HT on cell-mediated immunity and on the inflammatory response system (IRS) is still a matter of controversy. Some studies show that 5-HT has immunosuppressive effects. Devoino et al. (1968) reported that substances, which have the property to increase 5-HT concentrations, inhibit immunogenesis and antibody production in rodents. 5-HT may suppress delayed hypersensitivity and transplantation immunity (for review see Devoino and Morozova 1988). Bonnet et al. (1984) found that 5-HT suppresses murine lymphocytic response to phytohemagglutinin A (PHA) and/or allogeneic cells. p-Chlorophenylalanine (PCPA), an inhibitor of 5-HT synthesis, enhances the production of antibodies . Other immune functions, however, may be stimulated by 5-HT. For example, cutaneous injection of 5-HT can initiate a delayed-type hypersensitivity reaction through local recruitment and activation of CD4 ϩ T-helper cells (Ptak et al. 1991). Low doses (100 ng/ml) of exogenously added 5-HT stimulate T cell proliferation in response to interleukin-2 (IL-2) (Young et al. 1993; Young and Mathews 1995). Enhancement of murine T-cell blastogenesis by 5-HT has b...

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Serotonin inhibition of tumor necrosis factor-α synthesis by human monocytes

Cited by 75 publications

References 20 publications

Serotonin and histamine mediate gastroprotective effect of fluoxetine against experimentally-induced ulcers in rats

Serotonin and histamine mediate gastroprotective effect of fluoxetine against experimentally-induced ulcers in rats

Serotonin Skews Human Macrophage Polarization through HTR2B and HTR7

Effects of Serotonin and Serotonergic Agonists and Antagonists on the Production of Interferon-γ and Interleukin-10

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