SUPPRESSION OF EXPERIMENTAL ALLERGIC NEURITIS BY AN ANTIBODY TO THE INTERCELLULAR-ADHESION MOLECULE ICAM-1

Experimental allergic (autoimmune) neuritis (EAN) was induced in Lewis rats either by inoculation with bovine spinal root myelin or injection of neuritogenic P2-specific T cells. Injection of a purified monoclonal antibody (1A-29) to the intercellular adhesion molecule-1 (ICAM-1) prevented or transiently suppressed myelin-induced EAN depending on the timing of antibody application. Administration of 1A-29 suppressed moderate adoptive transfer EAN (AT-EAN) but not severe AT-EAN. In contrast, treatment with phosphate buffered saline or an unrelated IgG1 had no effect on the course of the disease. Histological sections of the peripheral nervous system (PNS) showed a marked reduction of inflammatory infiltrates and perivascular demyelination in rats injected with IA-29. The effect of IA-29 on the concanavalin A (Con A)- and P2-dependent proliferation of neuritogenic P2-specific T cells was studied in vitro. Our data suggest that antibodies to ICAM-1 act on the induction and effector phase of the immune response by inhibiting both early interactions between immunocompetent cells after exposure to foreign antigen and transendothelial migration of primed T cells into the peripheral nerve. Treatment with antibodies to leucocyte adhesion molecules could be a useful therapeutic approach to autoimmune disease of the PNS.