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 injectio n of neuritogenic P2-specific T cells. Injection of a purified monoclo nal antibody (1A-29) to the intercellular adhesion molecule-1 (ICAM-1) prevented or transiently suppressed myelin-induced EAN depending on t he timing of antibody application. Administration of 1A-29 suppressed moderate adoptive transfer EAN (AT-EAN) but not severe AT-EAN. In cont rast, treatment with phosphate buffered saline or an unrelated IgG1 ha d no effect on the course of the disease. Histological sections of the peripheral nervous system (PNS) showed a marked reduction of inflamma tory infiltrates and perivascular demyelination in rats injected with IA-29. The effect of IA-29 on the concanavalin A (Con A)- and P2-depen dent 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 in teractions between immunocompetent cells after exposure to foreign ant igen and transendothelial migration of primed T cells into the periphe ral nerve. Treatment with antibodies to leucocyte adhesion molecules c ould be a useful therapeutic approach to autoimmune disease of the PNS .