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.
Soilu-Hänninen
M
M
Department of Virology, University of Turku, Finland. merja.soilu-hanninen@utu.fi
Röyttä
M
M
Salmi
A
A
Salonen
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000956:Antigens, Viral / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy* / Q000821:virology; D007150:Immunohistochemistry; D007167:Immunotherapy; D039041:Integrin alpha4beta1; D019012:Integrin beta1 / Q000276:immunology; D016023:Integrins / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D012672:Semliki forest virus / Q000276:immunology
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D016177:Macrophage-1 Antigen; D016201:Receptors, Lymphocyte Homing; D018799:Intercellular Adhesion Molecule-1