Intrathecal administration of endothelin-1 receptor antagonist ameliorates autoimmune encephalomyelitis in Lewis rats.

The role of endothelin-1 (ET-1) in the development of experimental autoimmune encephalomyelitis (EAE) was studied by the blocking the action of ET-1 with a receptor antagonist, BQ-123. Intrathecal administration of BQ-123 significantly ameliorated EAE progression at the peak stage of EAE (p<0.05). By immunohistochemistry, ED-1-positive macrophages in EAE lesions were identified as major producers of ET-1, whereas the immunoreactivity of ET-1 on brain cells, such as astrocytes, was dramatically increased in accordance with the progression of EAE. This study points to a putative pro-1nflammatory 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 neurological disorders.