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
N1 - Funding Information:
This study was supported by grant 6P05A 076 20 from the State Committee for Scientific Research, Warszawa, Poland.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
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 - Serotonin
KW - Tumor necrosis factor
KW - mCPP
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U2 - 10.1016/j.psychres.2004.01.014
DO - 10.1016/j.psychres.2004.01.014
M3 - Article
C2 - 15892984
AN - SCOPUS:18844378658
VL - 134
SP - 251
EP - 258
JO - Psychiatry Research
JF - Psychiatry Research
SN - 0165-1781
IS - 3
ER -