A MONOCLONAL-ANTIBODY TO ALPHA-4-INTEGRIN REVERSES THE MR-DETECTABLE SIGNS OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN THE GUINEA-PIG

Experimental allergic encephalomyelitis (EAE) is a T cell-mediated aut oimmune disease of the CNS characterized by blood-brain barrier breakd own, cerebral edema formation, lymphocyte infiltration, and demyelinat ion, and is used as an animal model of multiple sclerosis (MS), MR ima ging is important for the diagnosis of MS and for the evaluation of po tential new therapies, In this study, T2-weighted and T1-weighted cont rast-enhanced MR imaging was used to evaluate the effectiveness of an antiadhesion therapy in EAE, Leukocyte-endothelial adhesion at the blo od-brain barrier is considered an essential step in the mediation of C NS leukocyte infiltration in EAE, AN100226m, a monoclonal antibody to alpha 4 integrin has been previously shown to reverse the clinical and histologic signs of EAE by blocking this interaction, In the present study, AN100226m treatment in acute EAE significantly decreased contra st enhancement of the CNS parenchyma indicating closure of the blood-b rain barrier, The percentage of pixels due to leakage of contrast mate rial in T1-weighted images decreased to <4% in AN100226m-treated anima ls whereas it was increased to 15% in control animals (P < .05, Mann-W hitney rank sum test), A decrease in CNS abnormalities associated with cerebral edema and inflammation was also observed on T2-weighted imag es (p < .05, Mann-Whitney rank sum test), Thus, an antibody to alpha 4 integrin reversed the blood-brain barrier permeability changes charac teristic of acute EAE, In addition, the further accumulation of inflam matory edema was prevented and prexisting edema was resolved.