ANTIADHESION MOLECULE THERAPY IN EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Based on previous observations showing that inflammatory episodes in t he central nervous system (CNS) of SJL/J mice with adoptively transfer red experimental allergic encephalomyelitis (EAE) are associated with a concomitant upregulation of adhesion-related molecules around CNS bl ood vessels, the present study was undertaken to block the development of EAE with injections of monoclonal antibodies (mAbs) to two differe nt adhesion molecules. The mAbs selected were directed against interce llular adhesion molecule-I (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) and were administered at different doses (50 mug-I mg), as single and multiple injections, and at various time points pos t-transfer of myelin basic protein-specific lymphocytes. Although one group of EAE mice given alphaLFA-1 displayed adverse effects after tre atment, on the whole, neither mAb had a statistically significant effe ct on the outcome of EAE in this murine model. There was, however, dow n-regulation in the CNS of the respective adhesion molecules after tre atment. Whether the lack of beneficial effect was related to the stage of EAE at which the mAbs were administered, remains to be proven. Thi s is the first report suggesting that alphaICAM-1 and alphaLFA-1 mAbs might have opposite effects (i.e. ameliorating or worsening) upon muri ne EAE and the different effect of alphaLFA-1 might be related to this molecule being involved in more cell signalling mechanisms than ICAM- 1.