Article

Inflammation Research

, Volume 46, Issue 9, pp 332-335

First online:

Benzydamine protection in a mouse model of endotoxemia

  • A. GuglielmottiAffiliated withLaboratory of Immunopharmacology, Angelini Ricerche, P.le della Stazione, I-00040 S. Palomba-Pomezia, Rome, Italy, Fax +39 6 91984597
  • , L. AquiliniAffiliated withLaboratory of Immunopharmacology, Angelini Ricerche, P.le della Stazione, I-00040 S. Palomba-Pomezia, Rome, Italy, Fax +39 6 91984597
  • , M. T. RosignoliAffiliated withLaboratory of Immunopharmacology, Angelini Ricerche, P.le della Stazione, I-00040 S. Palomba-Pomezia, Rome, Italy, Fax +39 6 91984597
  • , C. LandolfiAffiliated withLaboratory of Immunopharmacology, Angelini Ricerche, P.le della Stazione, I-00040 S. Palomba-Pomezia, Rome, Italy, Fax +39 6 91984597
  • , L. SoldoAffiliated withLaboratory of Immunopharmacology, Angelini Ricerche, P.le della Stazione, I-00040 S. Palomba-Pomezia, Rome, Italy, Fax +39 6 91984597
  • , I. ColettaAffiliated withLaboratory of Immunopharmacology, Angelini Ricerche, P.le della Stazione, I-00040 S. Palomba-Pomezia, Rome, Italy, Fax +39 6 91984597
  • , M. PinzaAffiliated withLaboratory of Immunopharmacology, Angelini Ricerche, P.le della Stazione, I-00040 S. Palomba-Pomezia, Rome, Italy, Fax +39 6 91984597

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Abstract.

Objective: Previous studies have shown that benzydamine (40 mg/kg s.c.) is able to inhibit tumor necrosis factor (TNF) production and to reduce mouse lethality when administered before or concomitantly with LPS. The present study was designed to further investigate benzydamine activity against LPS-induced toxicity in terms of potency and therapeutic effects.¶Methods: Female Balb/c mice were used. A dose-response curve of animal lethality versus endotoxin dose was performed (LD50 = 45 μg/mouse). Therapeutic effects were studied selecting the dose of LPS to achieve an LD100 (160 μg/mouse). Mortality was assessed daily and mice were followed for 8 days. The potential mode of action of therapeutically administered benzydamine was also investigated. TNFα and IL-1β levels were measured, at 5 h after LPS injection, both in sera and in lungs. Moreover, the drug was assayed in a TNF-dependent cytoxicity test.¶Results: Benzydamine, administered at 20 mg/kg s.c. simultaneously with the endotoxin, significantly increased LPS LD50 up to 230 μg/mouse (p < 0.05). Moreover, the drug significantly protected mice against LPS-induced lethality when administered either 30 min or 4 h after endotoxin injection (p < 0.001). Benzydamine, therapeutically administered at 20 mg/kg s.c., significantly reduced TNFα and IL-1β production induced by LPS both in serum and lungs and it was shown to inhibit TNF-dependent cytoxicity on L929 cells.¶Conclusions: These results clearly demonstrate the therapeutic activity of benzydamine in a simple model of endotoxic shock. Available data confirm the potential role of benzydamine as an anti-cytokine agent and provide suggestions for novel therapeutic applications of this anti-inflammatory drug.

Key words: Endotoxic shock — LPS — Mice — Inflammatory cytokines — TNFα