Immunomodulatory effects of the ether phospholipid edelfosine in experimental autoimmune encephalomyelitis

Pierre Abramowski; Karin Steinbach; Axel R Zander; Roland Martin

doi:10.1016/j.jneuroim.2014.07.007

Immunomodulatory effects of the ether phospholipid edelfosine in experimental autoimmune encephalomyelitis

J Neuroimmunol. 2014 Sep 15;274(1-2):111-24. doi: 10.1016/j.jneuroim.2014.07.007. Epub 2014 Jul 21.

Authors

Pierre Abramowski¹, Karin Steinbach², Axel R Zander³, Roland Martin⁴

Affiliations

¹ Institute for Neuroimmunology and Clinical MS Research (inims), Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany; Research Department Cell and Gene Therapy, Clinic for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
² Institute for Neuroimmunology and Clinical MS Research (inims), Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany; Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1 Rue Michel Servet, 1211 Geneva, Switzerland.
³ Department for Stem Cell Transplantation, University Cancer Center Hamburg (UCCH), Martinistr. 52, 20246 Hamburg, Germany.
⁴ Institute for Neuroimmunology and Clinical MS Research (inims), Center for Molecular Neurobiology (ZMNH), University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany; Neuroimmunology and MS Research (nims), Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland. Electronic address: roland.martin@usz.ch.

PMID: 25086877
DOI: 10.1016/j.jneuroim.2014.07.007

Abstract

The 2-lysophosphatidylcholine analog edelfosine induces apoptosis in highly proliferating cells, e.g. activated immune cells. We examined mechanisms of action of edelfosine on immune functions in experimental autoimmune encephalomyelitis, a well-accepted animal model for multiple sclerosis. We observed activated caspase-3 expression in lymphoid organs and the central nervous system; however, edelfosine did not induce global apoptosis. Edelfosine improved the disease course and led to reduced frequencies of CD4(+) T cells infiltrating into the central nervous system. Our data suggest edelfosine as an interesting treatment candidate for multiple sclerosis.

Keywords: Apoptosis; Edelfosine; Experimental autoimmune encephalomyelitis; Multiple sclerosis; T cells.

Publication types

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

MeSH terms

Animals
Apoptosis / drug effects
Apoptosis / immunology
Cell Proliferation / drug effects
Cells, Cultured
Disease Models, Animal
Encephalomyelitis, Autoimmune, Experimental / drug therapy*
Encephalomyelitis, Autoimmune, Experimental / immunology
Female
Immunologic Factors / immunology*
Male
Mice
Mice, Inbred C57BL
Multiple Sclerosis / drug therapy
Multiple Sclerosis / immunology
Phosphodiesterase Inhibitors / immunology
Phosphodiesterase Inhibitors / pharmacology
Phospholipid Ethers / immunology
Phospholipid Ethers / pharmacology*
T-Lymphocytes / cytology
T-Lymphocytes / drug effects
T-Lymphocytes / immunology

Substances

Immunologic Factors
Phosphodiesterase Inhibitors
Phospholipid Ethers
edelfosine