Abstract
Serotonin (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 (a 5-HT1A agonist), m-chlorophenylpiperazine (mCPP; a 5-HT2A/2C agonist), and ritanserin (a 5-HT2A/2C antagonist) on the production rate of interferon-γ (IFNγ), a proinflammatory cytokine, and IL-10 by whole blood stimulated with polyclonal activators. The IFNγ/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 μg/mL, and 15 μg/mL significantly decreased the IFNγ/IL-10 ratio; 2) PCPA (5 μM) significantly suppressed the production of IFNγ and IL-10; 3) flesinoxan (15 ng/mL; 1.5 μg/mL) had no significant effects on the production of the above cytokines; and 4) mCPP (2.7 μg/mL) and ritanserin (5.0 μg/mL) suppressed the IFNγ/IL-10 ratio. It is concluded that intracellular 5-HT may be necessary for an optimal synthesis of IFNγ and IL-10, and that extracellular 5-HT concentrations at or above serum values may suppress the production of the proinflammatory cytokine IFNγ. The negative immunoregulatory effects of antidepressive drugs are probably not related to their serotonergic activities.
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Acknowledgements
The research reported was supported by the Flemish Community, Belgium; the Funds for Scientific Research, Vlaanderen, Belgium (FWO); the Clinical Research Center for Mental Health, (CRC-MH), Antwerp, Belgium; the Staglin Investigator Award (NARSAD, USA) to Dr. M. Maes, and grant no. PO5A098–12 from the Committee on Scientific Research, Poland. The assistance of E. Nowak, Mrs. M. Maes, and R. Bullock are acknowledged.
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Kubera, M., Kenis, G., Bosmans, E. et al. Effects of Serotonin and Serotonergic Agonists and Antagonists on the Production of Interferon-γ and Interleukin-10. Neuropsychopharmacol 23, 89–98 (2000). https://doi.org/10.1016/S0893-133X(99)00150-5
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DOI: https://doi.org/10.1016/S0893-133X(99)00150-5
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