Document Detail


Bevacizumab diminishes experimental autoimmune encephalomyelitis by inhibiting spinal cord angiogenesis and reducing peripheral T-cell responses.
MedLine Citation:
PMID:  23037326     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Angiogenesis in the animal model of multiple sclerosis experimental autoimmune encephalomyelitis (EAE) is regulated by vascular endothelial growth factor (VEGF) and angiopoietin-2. We determined whether VEGF blockade with the anti-VEGF monoclonal antibody bevacizumab could inhibit angiogenesis and affect peripheral pathogenic immune responses in EAE. Mice treated with bevacizumab from the time of onset of clinical signs showed reduced clinical and pathologic scores. Bevacizumab suppressed angiogenesis and reduced angiopoietin-2 expression at Day 21 but had no effect on VEGF upregulation at Day 14. Messenger RNA levels for the angiogenesis-related protein CD105 were increased at Day 14. Bevacizumab reduced vascular permeability in the spinal cord at Day 14 and Day 21. In peripheral lymph nodes, it induced retention of CD4-positive T cells and inhibited T-cell proliferation. It also reduced mononuclear cell infiltration into spinal cord and the relative proportion of T cells. Isolated lymphoid cells showed reduced secretion of the T-helper 17 (Th-17) cell cytokine interleukin 17 and the Th-1 cytokine interferon-γ. When bevacizumab was added to naive T cells or to antigen-stimulated T cells from mice with untreated EAE in vitro, it had no effect on proliferation or the secretion of interleukin 17 or interferon-γ. These data indicate that bevacizumab ameliorates vascular and T-cell responses during EAE, but its effects on T cells may be indirect, possibly by suppressing angiogenesis.
Authors:
Carolyn J MacMillan; Suzanne J Furlong; Carolyn D Doucette; Pei-Lin Chen; David W Hoskin; Alexander S Easton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuropathology and experimental neurology     Volume:  71     ISSN:  1554-6578     ISO Abbreviation:  J. Neuropathol. Exp. Neurol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-25     Completed Date:  2013-01-17     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  2985192R     Medline TA:  J Neuropathol Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  983-99     Citation Subset:  IM    
Affiliation:
Department of Pathology, Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inhibitors / pharmacology
Animals
Antibodies, Monoclonal, Humanized / pharmacology*
CD4-Positive T-Lymphocytes / drug effects*,  metabolism,  pathology
Disease Models, Animal
Encephalomyelitis, Autoimmune, Experimental / drug therapy*,  pathology
Epitopes, T-Lymphocyte / metabolism*
Female
Mice
Mice, Inbred C57BL
Neovascularization, Pathologic / drug therapy*,  pathology
Severity of Illness Index
Spinal Cord / blood supply*,  pathology
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal, Humanized; 0/Epitopes, T-Lymphocyte; 2S9ZZM9Q9V/bevacizumab

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