Effects of serotonin and serotonergic agonists and antagonists on the production of tumor necrosis factor alpha and interleukin-6.
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-alpha (TNFalpha), as well as the role of 5-HT(1A) and 5-HT(2) 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-HT(1A) agonist, m-chlorophenylpiperazine (mCPP), a 5-HT(2B/2C) agonist, and ritanserin, a 5-HT(2A/2C) antagonist, on the production of the above cytokines. We found that: (1) 5-HT, 15 microg/ml, significantly decreased IL-6 and TNFalpha production; (2) pCPA, 5 microM, significantly suppressed the production of IL-6 and TNFalpha; and (3) mCPP, 2.7 microg/ml, significantly increased the production of IL-6 and TNFalpha. It is concluded that intracellular 5-HT is necessary for optimal synthesis of IL-6 and TNFalpha; 5-HT in physiological concentrations may increase IL-6 and TNFalpha production by stimulating 5-HT(2) receptors; and extracellular 5-HT concentrations above the baseline physiological levels may suppress the production of the above cytokines.
Kubera
Marta
M
Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. Kubera@if-pan.krakow.pl
Maes
Michael
M
Kenis
Gunter
G
Kim
Yong-Ku
YK
Lasoń
Władysław
W
D000328:Adult; D003866:Depressive Disorder / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D006801:Humans; D007121:Immunocompetence / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology; D044403:Receptor, Serotonin, 5-HT2B / Q000502:physiology; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015850:Interleukin-6; D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014409:Tumor Necrosis Factor-alpha; D044282:Receptor, Serotonin, 5-HT1A; D016713:Ritanserin; D012701:Serotonin; C056895:flesinoxan; D010134:Fenclonine; C015068:1-(3-chlorophenyl)piperazine