Efficacy of LL-37 and granulocyte colony-stimulating factor in a neutropenic murine sepsis due to Pseudomonas aeruginosa

Oscar Cirioni, Roberto Ghiselli, Linda Tomasinsig, Fiorenza Orlando, Carmela Silvestri, Barbara Skerlavaj, Alessandra Riva, Marco Rocchi, Vittorio Saba, Margherita Zanetti, Giorgio Scalise, Andrea Giacometti

Research output: Contribution to journalArticle

Abstract

A promising therapeutic strategy for the management of severe Pseudomonas infection in neutropenic patients may result from the coadministration of colony-stimulating factors (CSFs) that help maintain immune competence and antimicrobial peptides, a novel generation of adjunctive therapeutic agents with antimicrobial and anti-inflammatory properties. A promising peptide with these properties is LL-37, the only member of the cathelicidin family of antimicrobial peptides found in humans. BALB/c male mice were rendered neutropenic by intraperitoneal administration of cyclophosphamide on days -4 and -2 preinfection. Septic shock was induced at time 0 by intraperitoneal injection of 2 × 1010 colony-forming units of P. aeruginosa American Type Culture Collection (ATCC) 27853. All animals were randomized to receive intravenously isotonic sodium chloride solution, 1 mg/kg of LL-37, 20 mg/kg of imipenem, 0.1 mg/kg of granulocyte CSF (G-CSF), 1 mg/kg of LL-37 + 0.1 mg/kg of G-CSF, or 20 mg/kg of imipenem + 0.1 mg/kg of G-CSF. Lethality and bacterial growth in blood, peritoneum, spleen, liver, and kidney were evaluated. All regimens were significantly superior to controls at reducing the mouse lethality rate and bacterial burden in organs. Particularly, the combination between LL-37 and G-CSF was the most effective in protecting neutropenic mice from the onset of sepsis and in vitro significantly reduced the apoptosis of neutrophils. Combination therapy between LL-37 and G-CSF is a promising therapeutic strategy for the management of severe Pseudomonas infection complicated by neutropenia.

Original languageEnglish
Pages (from-to)443-448
Number of pages6
JournalShock
Volume30
Issue number4
DOIs
Publication statusPublished - Oct 2008

Keywords

  • Cathelicidin
  • G-CSF
  • Gram-negative sepsis
  • LL-37
  • Neutropenia

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine

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    Cirioni, O., Ghiselli, R., Tomasinsig, L., Orlando, F., Silvestri, C., Skerlavaj, B., Riva, A., Rocchi, M., Saba, V., Zanetti, M., Scalise, G., & Giacometti, A. (2008). Efficacy of LL-37 and granulocyte colony-stimulating factor in a neutropenic murine sepsis due to Pseudomonas aeruginosa. Shock, 30(4), 443-448. https://doi.org/10.1097/SHK.0b013e31816d2269