The role of dopamine in the modulation of monocyte-induced Th17- and Th1-immune response in multiple sclerosis

Int Immunopharmacol. 2024 Aug 20:137:112540. doi: 10.1016/j.intimp.2024.112540. Epub 2024 Jun 22.

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with autoimmune mechanism of development. The investigation of neuroimmune interaction is one of the most developing directions in MS pathogenesis study. Catecholamines are direct mediators of this interaction and can be involved in the pathogenesis of MS by modulating cells of both innate and adaptive immune systems. The aim of this study was to investigate the influence of dopamine and norepinephrine on the ability of monocytes of patients with relapsing-remitting MS, to induce Th17- and Th1-immune response, which play a crucial role in the autoimmunity of the CNS. We found, that both dopamine and norepinephrine modulate the production of Th17- (IL-23, IL-1β, and IL-6) and Th1-promoting (IL-12p70) cytokines by activated peripheral blood mononuclear cells or CD14+ monocytes in patients with MS and in healthy subjects. We also found the inhibitory effect of dopamine and norepinephrine on monocyte-induced production of IL-17 and IFN-γ by autologous CD4+ T-cells in both groups. Finally, the multidirectional role of D1- and D2-like dopaminergic receptors in the modulatory effect of dopamine on the ability of CD14+ monocytes to activate CD4+ T-cells was established, expanding the potential role of dopamine in the neuroimmune interaction.

Keywords: Dopamine; Monocytes; Multiple sclerosis; Neuroimmune interaction; Th17- and Th1-cells.

MeSH terms

  • Adult
  • Cells, Cultured
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dopamine* / metabolism
  • Female
  • Humans
  • Lipopolysaccharide Receptors / metabolism
  • Male
  • Middle Aged
  • Monocytes* / immunology
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Norepinephrine* / pharmacology
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / immunology
  • Receptors, Dopamine D2 / metabolism
  • Th1 Cells* / immunology
  • Th17 Cells* / immunology
  • Young Adult

Substances

  • Dopamine
  • Norepinephrine
  • Cytokines
  • Receptors, Dopamine D1
  • Lipopolysaccharide Receptors
  • Receptors, Dopamine D2