Substance P induces tumor necrosis factor in an ex vivo model system Article

Nair, MPN, Schwartz, SA. (1995). Substance P induces tumor necrosis factor in an ex vivo model system . Cellular Immunology, 166(2), 286-290. 10.1006/cimm.1995.9969

cited authors

  • Nair, MPN; Schwartz, SA

authors

abstract

  • Many studies have shown that tumor necrosis factor (TNF) is a potent soluble mediator of immunoregulation and inflammation. Neuropeptide substance P (SP) has been known to exert significant influence on production of certain inflammatory cytokine by immune cells. Immunopathogenic mechanism underlying the effect of neuropeptide substance P (SP) and the specific amino acid sequence of SP that induces TNF has not been clearly studied. Employing ex vivo and in vitro model systems, we investigated the direct effect of different sequences of SP on TNF secretion by whole blood and separated total mononuclear cells. Aliquots of blood samples (1 ml) or Ficoll-Hypaque-separated total mononuclear cells (1 x 106/ml) were cultured with different concentrations of SP and its sequences (SP 1-4, SP 4-11) or vasoactive intestinal peptide (VIP) for 24 hr at 37°C. Plasma samples and culture supernatants were assayed for TNF levels in a bioassay using a TNF-sensitive WEHI 164 subclone 13 cell line. Plasma from blood samples or lymphocytes treated with whole SP and SP 4-11 at 10-7, 10-8, and 10-9M concentrations induced significant production of TNF compared to negligible levels of TNF produced by SP 1-4-treated and untreated cultures. VIP at all concentrations tested did not induce TNF production and was similar to untreated control cultures. Separated mononuclear cells also produced significant levels of TNF in response to SP and SP 4-11. Anti-TNF-α antibodies neutralized the TNF induced by SP 4-11 in plasma. These studies suggest that an ex vivo system using whole blood may be an ideal model to study the effects of SP on TNF production. These studies also demonstrated that the TNF inducing activity of SP resides in the region containing amino acids 4 to 11. © 1995 Academic Press. All rights reserved.

publication date

  • January 1, 1995

published in

Digital Object Identifier (DOI)

start page

  • 286

end page

  • 290

volume

  • 166

issue

  • 2