Intrathecal administration of endothelin-1 receptor antagonist amelioratesautoimmune encephalomyelitis in Lewis rats

The role of endothelin-1 (ET-1) in the development of experimental autoimmu ne encephalomyelitis (EAE) was studied by the blocking the action of ET-1 w ith a receptor antagonist, BQ-123. Intrathecal administration of BQ-123 sig nificantly ameliorated EAE progression at the peak stage of EAE (P<0.05). B y immunohistochemistry, ED-1-positive macrophages in EAE lesions were ident ified as major producers of ET-1, whereas the immunoreactivity of ET-1 on b rain cells, such as astrocytes, was dramatically increased in accordance wi th the progression of EAE. This study points to a putative pro-inflammatory role for ET-1 in the pathogenesis of EAE. One possible application for the ET-1 receptor antagonist might be helpful in the therapy, of autoimmune ne urological disorders. NeuroReport 12:1465-1468 (C) 2001 Lippincott Williams & Wilkins.