Suppression of autoimmune encephalomyelitis by a neurokinin-1 receptor antagonist--a putative role for substance P in CNS inflammation.
J Neuroimmunol
; 179(1-2): 1-8, 2006 Oct.
Article
en En
| MEDLINE
| ID: mdl-16904192
ABSTRACT
Substance P (SP) is an excitatory neurotransmitter in the central and peripheral nervous system. Most of its physiological functions are mediated through binding to the neurokinin-1 receptor (NK-1R). Recently, proinflammatory properties of SP have been described. In this study we utilized T cell transfer experimental autoimmune encephalomyelitis (EAE) to investigate the role of SP in CNS autoimmune disease. Treatment with the NK-1R antagonist CP-96,345 dramatically reduced clinical and histological signs of EAE if administered before disease onset. The protective effect of CP96,345 treatment was related to a reduced expression of the adhesion molecules ICAM-1 and VCAM-1 on CNS endothelia. The cellular composition or activation status of splenocytes was not affected by CP-96,345 administration, while the secretion of proinflammatory Th1 cytokines was reduced in treated animals. Th2 cytokines remained largely unaffected by NK-1 receptor antagonist treatment. In summary, our findings suggest that the protective effect of CP96,345 treatment is mediated by stabilization of the blood-brain barrier and suppression of Th1 immunity.
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Compuestos de Bifenilo
/
Sustancia P
/
Sistema Nervioso Central
/
Antiinflamatorios no Esteroideos
/
Encefalomielitis Autoinmune Experimental
/
Antagonistas del Receptor de Neuroquinina-1
Límite:
Animals
Idioma:
En
Revista:
J Neuroimmunol
Año:
2006
Tipo del documento:
Article
País de afiliación:
Alemania