Effects of serotonin and serotonergic agonists and antagonists on the production of tumor necrosis factor α and interleukin-6

Marta Kubera, Michael Maes, Gunter Kenis, Yong Ku Kim, Władysław Lasoń

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Serotonin (5-HT) is a neurotransmitter and immune modulator. The effect of 5-HT on the production of cytokines by human macrophages and lymphocytes is poorly recognized. In the present article we examine the role of 5-HT in modulating the production of two pro-inflammatory cytokines, i.e. interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα), as well as the role of 5-HT1A and 5-HT2 receptors in this process. The specific aims were to examine the effects of 5-HT, p-chlorophenylalanine (PCPA), a 5-HT depleting agent, flesinoxan, a 5-HT1A agonist, m- chlorophenylpiperazine (mCPP), a 5-HT2B/2C agonist, and ritanserin, a 5-HT2A/2C antagonist, on the production of the above cytokines. We found that: (1) 5-HT, 15 μg/ml, significantly decreased IL-6 and TNFα production; (2) pCPA, 5 μM, significantly suppressed the production of IL-6 and TNFα; and (3) mCPP, 2.7 μg/ml, significantly increased the production of IL-6 and TNFα. It is concluded that intracellular 5-HT is necessary for optimal synthesis of IL-6 and TNFα; 5-HT in physiological concentrations may increase IL-6 and TNFα production by stimulating 5-HT2 receptors; and extracellular 5-HT concentrations above the baseline physiological levels may suppress the production of the above cytokines.

Original languageEnglish
Pages (from-to)251-258
Number of pages8
JournalPsychiatry Research
Volume134
Issue number3
DOIs
Publication statusPublished - 2005 Apr 30

Fingerprint

Serotonin Receptor Agonists
Serotonin Antagonists
Interleukin-6
Serotonin
Tumor Necrosis Factor-alpha
Cytokines
Serotonin 5-HT2 Receptor Agonists
Ritanserin
Fenclonine
Serotonin 5-HT1 Receptor Agonists
Serotonin 5-HT2 Receptor Antagonists
Receptor, Serotonin, 5-HT1A
Neurotransmitter Agents
Macrophages
Lymphocytes

Keywords

  • 5-HT receptor
  • Cytokines
  • Flesinoxan
  • Interferon
  • mCPP
  • Serotonin
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Effects of serotonin and serotonergic agonists and antagonists on the production of tumor necrosis factor α and interleukin-6. / Kubera, Marta; Maes, Michael; Kenis, Gunter; Kim, Yong Ku; Lasoń, Władysław.

In: Psychiatry Research, Vol. 134, No. 3, 30.04.2005, p. 251-258.

Research output: Contribution to journalArticle

Kubera, Marta ; Maes, Michael ; Kenis, Gunter ; Kim, Yong Ku ; Lasoń, Władysław. / Effects of serotonin and serotonergic agonists and antagonists on the production of tumor necrosis factor α and interleukin-6. In: Psychiatry Research. 2005 ; Vol. 134, No. 3. pp. 251-258.
@article{fae07ddff244408d8da06a34a78fa421,
title = "Effects of serotonin and serotonergic agonists and antagonists on the production of tumor necrosis factor α and interleukin-6",
abstract = "Serotonin (5-HT) is a neurotransmitter and immune modulator. The effect of 5-HT on the production of cytokines by human macrophages and lymphocytes is poorly recognized. In the present article we examine the role of 5-HT in modulating the production of two pro-inflammatory cytokines, i.e. interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα), as well as the role of 5-HT1A and 5-HT2 receptors in this process. The specific aims were to examine the effects of 5-HT, p-chlorophenylalanine (PCPA), a 5-HT depleting agent, flesinoxan, a 5-HT1A agonist, m- chlorophenylpiperazine (mCPP), a 5-HT2B/2C agonist, and ritanserin, a 5-HT2A/2C antagonist, on the production of the above cytokines. We found that: (1) 5-HT, 15 μg/ml, significantly decreased IL-6 and TNFα production; (2) pCPA, 5 μM, significantly suppressed the production of IL-6 and TNFα; and (3) mCPP, 2.7 μg/ml, significantly increased the production of IL-6 and TNFα. It is concluded that intracellular 5-HT is necessary for optimal synthesis of IL-6 and TNFα; 5-HT in physiological concentrations may increase IL-6 and TNFα production by stimulating 5-HT2 receptors; and extracellular 5-HT concentrations above the baseline physiological levels may suppress the production of the above cytokines.",
keywords = "5-HT receptor, Cytokines, Flesinoxan, Interferon, mCPP, Serotonin, Tumor necrosis factor",
author = "Marta Kubera and Michael Maes and Gunter Kenis and Kim, {Yong Ku} and Władysław Lasoń",
year = "2005",
month = "4",
day = "30",
doi = "10.1016/j.psychres.2004.01.014",
language = "English",
volume = "134",
pages = "251--258",
journal = "Psychiatry Research",
issn = "0165-1781",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

TY - JOUR

T1 - Effects of serotonin and serotonergic agonists and antagonists on the production of tumor necrosis factor α and interleukin-6

AU - Kubera, Marta

AU - Maes, Michael

AU - Kenis, Gunter

AU - Kim, Yong Ku

AU - Lasoń, Władysław

PY - 2005/4/30

Y1 - 2005/4/30

N2 - Serotonin (5-HT) is a neurotransmitter and immune modulator. The effect of 5-HT on the production of cytokines by human macrophages and lymphocytes is poorly recognized. In the present article we examine the role of 5-HT in modulating the production of two pro-inflammatory cytokines, i.e. interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα), as well as the role of 5-HT1A and 5-HT2 receptors in this process. The specific aims were to examine the effects of 5-HT, p-chlorophenylalanine (PCPA), a 5-HT depleting agent, flesinoxan, a 5-HT1A agonist, m- chlorophenylpiperazine (mCPP), a 5-HT2B/2C agonist, and ritanserin, a 5-HT2A/2C antagonist, on the production of the above cytokines. We found that: (1) 5-HT, 15 μg/ml, significantly decreased IL-6 and TNFα production; (2) pCPA, 5 μM, significantly suppressed the production of IL-6 and TNFα; and (3) mCPP, 2.7 μg/ml, significantly increased the production of IL-6 and TNFα. It is concluded that intracellular 5-HT is necessary for optimal synthesis of IL-6 and TNFα; 5-HT in physiological concentrations may increase IL-6 and TNFα production by stimulating 5-HT2 receptors; and extracellular 5-HT concentrations above the baseline physiological levels may suppress the production of the above cytokines.

AB - Serotonin (5-HT) is a neurotransmitter and immune modulator. The effect of 5-HT on the production of cytokines by human macrophages and lymphocytes is poorly recognized. In the present article we examine the role of 5-HT in modulating the production of two pro-inflammatory cytokines, i.e. interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα), as well as the role of 5-HT1A and 5-HT2 receptors in this process. The specific aims were to examine the effects of 5-HT, p-chlorophenylalanine (PCPA), a 5-HT depleting agent, flesinoxan, a 5-HT1A agonist, m- chlorophenylpiperazine (mCPP), a 5-HT2B/2C agonist, and ritanserin, a 5-HT2A/2C antagonist, on the production of the above cytokines. We found that: (1) 5-HT, 15 μg/ml, significantly decreased IL-6 and TNFα production; (2) pCPA, 5 μM, significantly suppressed the production of IL-6 and TNFα; and (3) mCPP, 2.7 μg/ml, significantly increased the production of IL-6 and TNFα. It is concluded that intracellular 5-HT is necessary for optimal synthesis of IL-6 and TNFα; 5-HT in physiological concentrations may increase IL-6 and TNFα production by stimulating 5-HT2 receptors; and extracellular 5-HT concentrations above the baseline physiological levels may suppress the production of the above cytokines.

KW - 5-HT receptor

KW - Cytokines

KW - Flesinoxan

KW - Interferon

KW - mCPP

KW - Serotonin

KW - Tumor necrosis factor

UR - http://www.scopus.com/inward/record.url?scp=18844378658&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18844378658&partnerID=8YFLogxK

U2 - 10.1016/j.psychres.2004.01.014

DO - 10.1016/j.psychres.2004.01.014

M3 - Article

VL - 134

SP - 251

EP - 258

JO - Psychiatry Research

JF - Psychiatry Research

SN - 0165-1781

IS - 3

ER -