EVIDENCE FOR A PROLONGED ROLE OF ALPHA(4) INTEGRIN THROUGHOUT ACTIVE EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

The leukocyte integrin receptor, alpha(4) beta(1), and its endothelial cell ligand, vascular cell adhesion molecule 1, appear to be of criti cal importance in the leukocyte trafficking that accompanies CNS damag e in experimental allergic encephalomyelitis (EAE). In this study, the persistence of the role for alpha(4) beta(1)/VCAM-1 in EAE was establ ished by observing antibody-mediated disease reversal up to 1 month fo llowing disease onset. Limited treatment with a monoclonal antibody ag ainst alpha(4) integrin, GG5/3, resulted in a significant decrease in both clinical and histopathologic signs. This was not observed in isot ype control experiments. In the latter phase of progressive disease, w idespread demyelination occurred in the animals that did not respond t o 6 days of anti-alpha(4) treatment. These results demonstrate an esse ntial role for alpha(4) beta(1) interactions throughout active EAE and illustrate the difference between reversible clinical deficits caused by edema and irreversible deficits associated with demyelination.