Inhibition of inflammatory cytokine production and protection against endotoxin toxicity by benzydamine

M. Sironi, P. Pozzi, N. Polentarutti, F. Benigni, I. Coletta, A. Guglielmotti, C. Milanese, P. Ghezzi, A. Vecchi, M. Pinza, A. Mantovani

Research output: Contribution to journalArticlepeer-review

Abstract

The present study was designed to assess the effect of N,N-dimethyl-3-[(1-benzyl-1H-indazol-3-yl)ossi]-1-propanamine (benzydamine) on in vivo and in vitro production of inflammatory cytokines. Benzydamine inhibited tumour necrosis factor-alpha (TNF-α) production in vitro by human lipopolysaccharide-stimulated monocytes with an ED50 of ~25 μM (12 donors). Under the same conditions, benzydamine had modest or no effect on production of interleukin (IL-1), IL-6 and IL-8. Inhibition of TNF-α production was not restricted to LPS in that similar results were obtained using inactivated streptococci. Inhibition of TNF production was associated with a modest (about 30% at 50 μM, 7 donors) reduction of mRNA. A similar inhibition of TNF-α production was also detected with mouse peritoneal macrophages. With mouse cells benzydamine also substantially inhibited IL-1 production in vitro. In vivo treatment with benzydamine (40 mg/kg s.c.) protected mice against LPS lethality. Protection against septic shock was observed when benzydamine was administered before or concomitantly with LPS. Protection against LPS toxicity was associated with a marked reduction of serum levels of TNF-α and IL-1β, whereas IL-6 was unaffected. Inhibition of inflammatory cytokine production may play a role in the anti-inflammatory activity of benzydamine and provide suggestions for novel therapeutic applications.

Original languageEnglish
Pages (from-to)710-716
Number of pages7
JournalCytokine
Volume8
Issue number9
DOIs
Publication statusPublished - Sep 1996

Keywords

  • Anti-inflammatory drug
  • Endotoxin toxicity inflammatory cytokines
  • TNF-α

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy

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