ENHANCED SECRETION OF SUBSTANCE-P BY CYTOKINE-STIMULATED RAT-BRAIN ENDOTHELIUM CULTURES

Substance P (SP) was analyzed in rat brain endothelium cultures after cytokine stimulation. SP secretion was found after stimulation with hi gh doses of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-a lpha (TNF-alpha). High doses of interferon-gamma (INF-gamma) had no ef fect on this secretion. Elevated SP release was found to be associated with mRNA expression of beta-preprotachykinin (beta-PPT), precursor o f SP, in the cells. Under cytokine stimulation, part of SP was bound t o brain endothelial cell surface, suggesting the existence of an autoc rine network for this neuropeptide. These findings suggest that SP map have an immunomodulatory action at the blood-brain barrier during inf lammatory and autoimmune processes in the central nervous system. (C) 1998 Elsevier Science B.V.