The role of 5-HT2B-receptors in fluoxetine-mediated modulation of Th17- and Th1-cells in multiple sclerosis

Anastasiya Sviridova; Vladimir Rogovskii; Vladimir Kudrin; Mikhail Pashenkov; Alexey Boyko; Mikhail Melnikov

doi:10.1016/j.jneuroim.2021.577608

The role of 5-HT_2B-receptors in fluoxetine-mediated modulation of Th17- and Th1-cells in multiple sclerosis

J Neuroimmunol. 2021 Jul 15:356:577608. doi: 10.1016/j.jneuroim.2021.577608. Epub 2021 May 12.

Authors

Anastasiya Sviridova¹, Vladimir Rogovskii², Vladimir Kudrin³, Mikhail Pashenkov⁴, Alexey Boyko¹, Mikhail Melnikov⁵

Affiliations

¹ Federal Center of Brain research and Neurotechnology of the Federal Medical-Biological Agency of Russia, Department of Neuroimmunology, Moscow, Russia; Pirogov Russian National Research Medical University, Department of Neurology, Neurosurgery and Medical Genetics, Moscow, Russia.
² Federal Center of Brain research and Neurotechnology of the Federal Medical-Biological Agency of Russia, Department of Neuroimmunology, Moscow, Russia; Pirogov Russian National Research Medical University, Department of Molecular Pharmacology and Radiobiology, Moscow, Russia.
³ V.V. Zakusov Research Institute of Pharmacology, Laboratory of Neurochemical Pharmacology Moscow, Russia.
⁴ National Research Center Institute of Immunology of the Federal Medical-Biological Agency of Russia, Laboratory of Clinical Immunology, Moscow, Russia.
⁵ Pirogov Russian National Research Medical University, Department of Neurology, Neurosurgery and Medical Genetics, Moscow, Russia; National Research Center Institute of Immunology of the Federal Medical-Biological Agency of Russia, Laboratory of Clinical Immunology, Moscow, Russia. Electronic address: medikms@yandex.ru.

PMID: 34000471
DOI: 10.1016/j.jneuroim.2021.577608

Abstract

Fluoxetine is a selective serotonin reuptake inhibitor, which also has an immunomodulatory effect. We investigated the effects of fluoxetine and serotonin (5-HT) on the pro-inflammatory Th17- and Th1-cells in 30 patients with relapsing-remitting MS and 20 healthy subjects. Fluoxetine and 5-HT suppressed IL-17, IFN-γ and GM-CSF production by stimulated СD4⁺ T-cells in both groups. Blockade of 5-HT_2B-receptors decreased the inhibitory effect of fluoxetine on cytokine production in MS patients. Finally, 5-HT_2B-receptor activation inhibits IL-17, IFN-γ and GM-CSF production in both groups. These data suggest an anti-inflammatory role for fluoxetine in MS, which could be mediated by the activation of 5-HT_2B-receptors.

Keywords: 5-HT; 5-HT(2B)-receptors; Fluoxetine; Multiple sclerosis; Th1-cells; Th17-cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Female
Fluoxetine / pharmacology
Fluoxetine / therapeutic use*
Humans
Male
Multiple Sclerosis / drug therapy*
Multiple Sclerosis / immunology
Multiple Sclerosis / metabolism
Receptor, Serotonin, 5-HT2B / immunology
Receptor, Serotonin, 5-HT2B / metabolism*
Selective Serotonin Reuptake Inhibitors / pharmacology
Selective Serotonin Reuptake Inhibitors / therapeutic use*
Serotonin 5-HT2 Receptor Agonists / pharmacology
Serotonin 5-HT2 Receptor Antagonists / pharmacology
Th1 Cells / drug effects*
Th1 Cells / immunology
Th1 Cells / metabolism
Th17 Cells / drug effects*
Th17 Cells / immunology
Th17 Cells / metabolism
Young Adult

Substances

Receptor, Serotonin, 5-HT2B
Serotonin 5-HT2 Receptor Agonists
Serotonin 5-HT2 Receptor Antagonists
Serotonin Uptake Inhibitors
Fluoxetine