Amelioration of ongoing experimental autoimmune encephalomyelitis with fluoxetine

J Neuroimmunol. 2017 Dec 15;313:77-81. doi: 10.1016/j.jneuroim.2017.10.012. Epub 2017 Oct 21.

Abstract

In patients with multiple sclerosis, the selective serotonin reuptake inhibitor, fluoxetine, resulted in less acute disease activity. We tested the immune modulating effects of fluoxetine in a mouse model of multiple sclerosis, i.e. experimental autoimmune encephalomyelitis (EAE). We show that fluoxetine delayed the onset of disease and reduced clinical paralysis in mice with established disease. Fluoxetine had abrogating effects on proliferation of immune cells and inflammatory cytokine production by both antigen-presenting cells and T cells. Specifically, in CD4 T cells, fluoxetine increased Fas-induced apoptosis. We conclude that fluoxetine possesses immune-modulating effects resulting in the amelioration of symptoms in EAE.

Keywords: EAE; Experimental autoimmune encephalomyelitis; Fluoxetine; Multiple sclerosis; Neuroinflammation; SSRI.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Apoptosis
  • CD11b Antigen / metabolism
  • Cell Death / drug effects
  • Cell Proliferation / drug effects
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Female
  • Fluoxetine / therapeutic use*
  • Freund's Adjuvant / adverse effects
  • Freund's Adjuvant / immunology
  • Macrophages / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Transgenic
  • Myelin Basic Protein / genetics
  • Myelin Proteolipid Protein / adverse effects
  • Myelin Proteolipid Protein / immunology
  • Peptide Fragments / adverse effects
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / pathology
  • fas Receptor / metabolism

Substances

  • Anti-Inflammatory Agents
  • CD11b Antigen
  • Cytokines
  • Fas protein, rat
  • Myelin Basic Protein
  • Myelin Proteolipid Protein
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • fas Receptor
  • myelin proteolipid protein (139-151)
  • Fluoxetine
  • Freund's Adjuvant