Anti-adhesion molecule therapy in experimental autoimmune encephalomyelitis.
Based on previous observations showing that inflammatory episodes in the central nervous system (CNS) of SJL/J mice with adoptively transferred experimental allergic encephalomyelitis (EAE) are associated with a concomitant upregulation of adhesion-related molecules around CNS blood vessels, the present study was undertaken to block the development of EAE with injections of monoclonal antibodies (mAbs) to two different adhesion molecules. The mAbs selected were directed against intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) and were administered at different doses (50 micrograms-1 mg), as single and multiple injections, and at various time points post-transfer of myelin basic protein-specific lymphocytes. Although one group of EAE mice given alpha LFA-1 displayed adverse effects after treatment, on the whole, neither mAb had a statistically significant effect on the outcome of EAE in this murine model. There was, however, down-regulation in the CNS of the respective adhesion molecules after treatment. Whether the lack of beneficial effect was related to the stage of EAE at which the mAbs were administered, remains to be proven. This is the first report suggesting that alpha ICAM-1 and alpha LFA-1 mAbs might have opposite effects (i.e. ameliorating or worsening) upon murine EAE and the different effect of alpha LFA-1 might be related to this molecule being involved in more cell signalling mechanisms than ICAM-1.
Cannella
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B
Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, NY 10461.
Cross
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AH
Raine
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CS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000628:therapy*; D005260:Female; D007116:Immunization, Passive; D007167:Immunotherapy; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1