Amelioration of ongoing experimental autoimmune encephalomyelitis with fluoxetine

Roopa Bhat; Sidharth Mahapatra; Robert C Axtell; Lawrence Steinman

doi:10.1016/j.jneuroim.2017.10.012

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.

Authors

Roopa Bhat¹, Sidharth Mahapatra², Robert C Axtell³, Lawrence Steinman⁴

Affiliations

¹ Bellevue Neurology, Bellevue, WA 98004, United States.
² Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE 68198, United States. Electronic address: [email protected].
³ Department of Arthritis and Clinical Immunology Research, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, United States.
⁴ Departments of Pediatrics and Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA 94305, United States.

PMID: 29153612
DOI: 10.1016/j.jneuroim.2017.10.012

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