RNAIII-inhibiting peptide in combination with the cathelicidin BMAP-28 reduces lethality in mouse models of staphylococcal sepsis

Roberto Ghiselli, Andrea Giacometti, Oscar Cirioni, Giorgio Dell'Acqua, Cristina Bergnach, Fiorenza Orlando, Federico Mocchegiani, Carmela Silvestri, Barbara Skerlavaj, Alberto Licci, Naomi Balaban, Margherita Zanetti, Giorgio Scalise, Vittorio Saba

Research output: Contribution to journalArticlepeer-review

Abstract

A mouse model of staphylococcal sepsis was used to evaluate the efficacy of RNAIII-inhibiting peptide (RIP) combined with the cathelicidin BMAP-28. Preliminary in vitro studies showed that both peptides, alone or combined, were able to inhibit the lipoteichoic acid-induced production of tumor necrosis factor α and nitric oxide by RAW 264.7 cells. For in vivo experiments, the main outcome measures were lethality, quantitative blood cultures, and detection of tumor necrosis factor α and interleukin 6 plasma levels. BALB/c mice were injected i.v. with 2.0 × 10 colony-forming units of live Staphylococcus aureus ATCC 25923 or with 5.0 × 10 heat-killed cells of the same strain. All animals were randomized to receive i.v. isotonic sodium chloride solution, 10-mg/kg RIP, alone or in combination with 2-mg/kg BMAP-28, 7-mg/kg imipenem, or 7-mg/kg vancomycin, immediately and at 6 hours after bacterial challenge. In in vivo experiments performed with live bacteria, all compounds reduced lethality rates and bacteremia when compared with controls. In general, combined-treated groups had significantly lower bacteremia when compared with single-treated groups. Lowest lethality rates and bacteremia were obtained when RIP was administered in combination with BMAP-28 or vancomycin. In the experiments performed using heat-killed organisms, only BMAP-28 demonstrated significant efficacy on lethality rates and cytokines plasma levels when compared with controls. RIP combined with BMAP-28 exhibited the highest efficacy on all main outcome measurements. These data were observed on both immediate and delayed treatments. These results highlight the capacity of RIP and BMAP-28 to reduce the septic effects of bacterial cell components and exotoxins, and suggest their potential use in the treatment of severe staphylococcus-associated sepsis.

Original languageEnglish
Pages (from-to)296-301
Number of pages6
JournalShock
Volume26
Issue number3
DOIs
Publication statusPublished - Sep 2006

Keywords

  • Antimicrobial peptide
  • BMAP-28
  • RIP
  • Septic shock
  • Staphylococcal sepsis

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

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