Bevacizumab diminishes experimental autoimmune encephalomyelitis by inhibiting spinal cord angiogenesis and reducing peripheral T-Cell responses

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Resumen

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-F. 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.

Idioma originalEnglish
Páginas (desde-hasta)983-999
Número de páginas17
PublicaciónJournal of Neuropathology and Experimental Neurology
Volumen71
N.º11
DOI
EstadoPublished - nov. 2012

ASJC Scopus Subject Areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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