Therapy with antibody against leukocyte integrin VLA-4 (CD49d) is effective and safe in virus-facilitated experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is facilitated in resistant BALB/c mice by intraperitoneal infection with an avirulent Semliki Forest virus (SFV-A7). Viral infection increases the incidence of EAE from 15-30% to 60-90% and speeds up appearance of paralysis from 24 to 14 days. In this paper, we describe treatment of virus-facilitated EAE with monoclonal antibodies (mAbs) against leukocyte and/or endothelial cell adhesion molecules. Therapy with mAb against ICAM-1 (intercellular adhesion molecule-1) had a modest effect, but caused hemorrhagic brain and spinal cord lesions. Therapy with mAb against Mac-1 (alpha M beta 2-integrin) was well tolerated but had no effect. Therapy with mAb against VLA-4 (alpha 4 beta 1-integrin) was safe, diminished both clinical and histopathological signs of EAE, decreased induction of VCAM-1 (vascular cell adhesion molecule-1) on brain vessels and diminished infiltration of VLA-4+ cells into the brain. The amount of viral antigen in the brain was not altered. We conclude that facilitation of leukocyte entry into the brain is a major mechanism for viral facilitation of EAE in the BALB/c mouse, and that facilitation can be inhibited by anti-adhesion therapy. This may have implications for treatment of relapses triggered by viral infections in multiple sclerosis.
AuthorsM Soilu-Hänninen, M Röyttä, A Salmi, R Salonen
JournalJournal of neuroimmunology (J Neuroimmunol) Vol. 72 Issue 1 Pg. 95-105 (Jan 1997) ISSN: 0165-5728 [Print] NETHERLANDS
PMID9003249 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Antigens, CD29
  • Antigens, Viral
  • Integrin alpha4beta1
  • Integrins
  • Macrophage-1 Antigen
  • Receptors, Lymphocyte Homing
  • Intercellular Adhesion Molecule-1
  • Animals
  • Antibodies, Monoclonal (pharmacology)
  • Antigens, CD29 (immunology)
  • Antigens, Viral (immunology)
  • Encephalomyelitis, Autoimmune, Experimental (immunology, therapy, virology)
  • Immunohistochemistry
  • Immunotherapy
  • Integrin alpha4beta1
  • Integrins (immunology)
  • Intercellular Adhesion Molecule-1 (immunology)
  • Macrophage-1 Antigen (chemistry, immunology)
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Lymphocyte Homing (immunology)
  • Semliki forest virus (immunology)

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