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 language | English |
|---|---|
| Pages (from-to) | 710-716 |
| Number of pages | 7 |
| Journal | Cytokine |
| Volume | 8 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 1996 |
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Keywords
- Anti-inflammatory drug
- Endotoxin toxicity inflammatory cytokines
- TNF-α
ASJC Scopus subject areas
- Endocrinology
- Molecular Biology
- Immunology
- Immunology and Allergy
Cite this
Inhibition of inflammatory cytokine production and protection against endotoxin toxicity by benzydamine. / Sironi, M.; Pozzi, P.; Polentarutti, N.; Benigni, F.; Coletta, I.; Guglielmotti, A.; Milanese, C.; Ghezzi, P.; Vecchi, A.; Pinza, M.; Mantovani, A.
In: Cytokine, Vol. 8, No. 9, 09.1996, p. 710-716.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of inflammatory cytokine production and protection against endotoxin toxicity by benzydamine
AU - Sironi, M.
AU - Pozzi, P.
AU - Polentarutti, N.
AU - Benigni, F.
AU - Coletta, I.
AU - Guglielmotti, A.
AU - Milanese, C.
AU - Ghezzi, P.
AU - Vecchi, A.
AU - Pinza, M.
AU - Mantovani, A.
PY - 1996/9
Y1 - 1996/9
N2 - 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.
AB - 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.
KW - Anti-inflammatory drug
KW - Endotoxin toxicity inflammatory cytokines
KW - TNF-α
UR - http://www.scopus.com/inward/record.url?scp=0030249568&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030249568&partnerID=8YFLogxK
U2 - 10.1006/cyto.1996.0094
DO - 10.1006/cyto.1996.0094
M3 - Article
C2 - 8932982
AN - SCOPUS:0030249568
VL - 8
SP - 710
EP - 716
JO - Cytokine
JF - Cytokine
SN - 1043-4666
IS - 9
ER -