Neuroactive steroids such as dehydroepiandrosterone sulfate and pregnenolone inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) production. Corticosteroids not only inhibit TNF production but their levels are increased in vivo after endotoxin injection, thus representing a feedback system that limits TNF production. We wondered whether the same could be true for neuroactive steroids. Thus, the possibility that neuroactive steroids might be increased concomitantly to TNF induction in vivo in mice treated with LPS was investigated. Increased plasma and hippocampal levels of allopregnanolone (but not of dehydroepiandrosterone or pregnenolone) were found 90 min after LPS injection. Allopregnanolone and progesterone (IC50 10(-7) and 10(-9) M, respectively) also inhibited TNF production by mouse peritoneal macrophages in vitro at concentrations in the range of those detected in vivo. These findings suggest that neuroactive steroids may act as endogenous inhibitors of cerebral and systemic TNF production.

Ghezzi, P., Di Santo, E., Sacco, S., Foddi, C., Barbaccia, M.l., Mennini, T. (2000). Neurosteroid levels are increased in vivo after LPS treatment and negatively regulate LPS-induced TNF production. EUROPEAN CYTOKINE NETWORK, 11(3), 464-469.

Neurosteroid levels are increased in vivo after LPS treatment and negatively regulate LPS-induced TNF production

BARBACCIA, MARIA LUISA;
2000-01-01

Abstract

Neuroactive steroids such as dehydroepiandrosterone sulfate and pregnenolone inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) production. Corticosteroids not only inhibit TNF production but their levels are increased in vivo after endotoxin injection, thus representing a feedback system that limits TNF production. We wondered whether the same could be true for neuroactive steroids. Thus, the possibility that neuroactive steroids might be increased concomitantly to TNF induction in vivo in mice treated with LPS was investigated. Increased plasma and hippocampal levels of allopregnanolone (but not of dehydroepiandrosterone or pregnenolone) were found 90 min after LPS injection. Allopregnanolone and progesterone (IC50 10(-7) and 10(-9) M, respectively) also inhibited TNF production by mouse peritoneal macrophages in vitro at concentrations in the range of those detected in vivo. These findings suggest that neuroactive steroids may act as endogenous inhibitors of cerebral and systemic TNF production.
2000
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14 - FARMACOLOGIA
English
Con Impact Factor ISI
neurosteroids; steroids; central nervous system; endocrinology; macrophages
6
Ghezzi, P., Di Santo, E., Sacco, S., Foddi, C., Barbaccia, M.l., Mennini, T. (2000). Neurosteroid levels are increased in vivo after LPS treatment and negatively regulate LPS-induced TNF production. EUROPEAN CYTOKINE NETWORK, 11(3), 464-469.
Ghezzi, P; Di Santo, E; Sacco, S; Foddi, C; Barbaccia, Ml; Mennini, T
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/49674
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 23
social impact