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Suppression of autoimmune encephalomyelitis by a neurokinin-1 receptor antagonist--a putative role for substance P in CNS inflammation.

Suppression of autoimmune encephalomyelitis by a neurokinin-1 receptor antagonist--a putative role for substance P in CNS inflammation.

Authors :
Nessler S
Stadelmann C
Bittner A
Schlegel K
Gronen F
Brueck W
Hemmer B
Sommer N
Source :
Journal of neuroimmunology [J Neuroimmunol] 2006 Oct; Vol. 179 (1-2), pp. 1-8. Date of Electronic Publication: 2006 Aug 10.
Publication Year :
2006

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.

Details

Language :
English
ISSN :
0165-5728
Volume :
179
Issue :
1-2
Database :
MEDLINE
Journal :
Journal of neuroimmunology
Publication Type :
Academic Journal
Accession number :
16904192
Full Text :
https://doi.org/10.1016/j.jneuroim.2006.06.026