Temporin A alone and in combination with imipenem reduces lethality in a mouse model of staphylococcal sepsis

Oscar Cirioni, Andrea Giacometti, Roberto Ghiselli, Wojciech Kamysz, Fiorenza Orlando, Federico Mocchegiani, Carmela Silvestri, Alberto Licci, Jerzy Łukasiak, Vittorio Saba, Giorgio Scalise

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Morbidity and mortality from staphylococcal toxic shock remain high, despite the availability of antibiotics to which the microorganism is sensitive. Methods. In in vitro experiments, the ability of temporin A to inhibit lipoteichoic acid-induced production of tumor necrosis factor (TNF)-α and nitric oxide (NO) was determined. Also, mouse models of staphylococcal sepsis were used to evaluate the efficacy of temporin A alone and in combination with imipenem. BALB/c mice were injected intravenously with live Staphylococcus aureus or heat-killed cells and then received either isotonic sodium chloride solution, 2 mg/kg temporin A, 7 mg/kg imipenem, or 2 mg/kg temporin A in combination with 7 mg/kg imipenem immediately and 6 h after challenge. The main outcome measures were lethality rates, plasma bacterial counts, and plasma TNF-α and interleukin (IL)-6 levels. Results. The in vitro experiments showed that temporin A did not cause TNF-α or NO release. In the in vivo experiments with live bacteria, both compounds reduced lethality rates and bacterial growth. Imipenem exhibited the highest efficacy. The combination-treated group had significantly lower bacterial counts than did the singly-treated groups and the lowest lethality rates. In the experiments with heat-killed cells, only temporin A demonstrated significant efficacy with respect to lethality and reduction of plasma TNF-α and IL-6 levels. Discussion. This study shows that temporin A can reduce the stimulatory effects of bacterial cell components and suggests that it may be beneficial in the treatment of severe staphylococcal sepsis.

Original languageEnglish
Pages (from-to)1613-1620
Number of pages8
JournalJournal of Infectious Diseases
Volume192
Issue number9
DOIs
Publication statusPublished - Nov 1 2005

ASJC Scopus subject areas

  • Immunology
  • Public Health, Environmental and Occupational Health

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