Granulocyte macrophage colony-stimulating factor: a new putative therapeutic target in multiple sclerosis.
Experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, can be induced by immunization with a number of myelin antigens. In particular, myelin oligodendrocyte glycoprotein, a central nervous system (CNS)-specific antigen expressed on the myelin surface, is able to induce a paralytic MS-like disease with extensive CNS inflammation and demyelination in several strains of animals. Although not well understood, the egress of immune cells into the CNS in EAE is governed by a complex interplay between pro and antiinflammatory cytokines and chemokines. The hematopoietic growth factor, granulocyte macrophage colony-stimulating factor (GM-CSF), is considered to play a central role in maintaining chronic inflammation. The present study was designed to investigate the previously unexplored role of GM-CSF in autoimmune-mediated demyelination. GM-CSF(-/)- mice are resistant to EAE, display decreased antigen-specific proliferation of splenocytes, and fail to sustain immune cell infiltrates in the CNS, thus revealing key activities for GM-CSF in the development of inflammatory demyelinating lesions and control of migration and/or proliferation of leukocytes within the CNS. These results hold implications for the pathogenesis of inflammatory and demyelinating diseases and may provide the basis for more effective therapies for inflammatory diseases, and more specifically for multiple sclerosis.
McQualter
J L
JL
Neuroimmunology Laboratory, Department of Biochemistry, La Trobe University, Victoria 3086, Australia.
Darwiche
R
R
Ewing
C
C
Onuki
M
M
Kay
T W
TW
Hamilton
J A
JA
Reid
H H
HH
Bernard
C C
CC
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000628:therapy*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000276:immunology*; D007113:Immunity, Innate; D007167:Immunotherapy; D051379:Mice; D016688:Mice, Inbred NOD; D008817:Mice, Mutant Strains; D009103:Multiple Sclerosis / Q000209:etiology / Q000628:therapy*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D013601:T-Lymphocytes / Q000276:immunology
D001323:Autoantibodies; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor