Abstract |
We investigated the efficacy of LL-37, the C-terminal part of the only cathelicidin in humans identified to date (termed human cationic antimicrobial protein), in three experimental rat models of gram-negative sepsis. Adult male Wistar rats (i) were given an intraperitoneal injection of 1 mg Escherichia coli 0111:B4 LPS, (ii) were given 2 x 10(10) CFU of Escherichia coli ATCC 25922, or (iii) had intra-abdominal sepsis induced via cecal ligation and puncture. For each model, all animals were randomized to receive intravenously isotonic sodium chloride solution, 1-mg/kg LL-37, 1-mg/kg polymyxin B, 20-mg/kg imipenem, or 60-mg/kg piperacillin. Lethality; growth of bacteria in blood, peritoneum, spleen, liver, and mesenteric lymph nodes; and endotoxin and tumor necrosis factor alpha ( TNF-alpha) concentrations in plasma were evaluated. All compounds reduced lethality compared to levels in controls. Endotoxin and TNF-alpha plasma levels were significantly higher in conventional antibiotic-treated rats than in LL-37- and polymyxin B-treated animals. All drugs tested significantly reduced bacterial growth compared to saline treatment. No statistically significant differences between LL-37 and polymyxin B were noted for antimicrobial and antiendotoxin activities. LL-37 and imipenem proved to be the most effective treatments in reducing all variables measured. Due to its multifunctional properties, LL-37 may become an important future consideration for the treatment of sepsis.
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Authors | Oscar Cirioni, Andrea Giacometti, Roberto Ghiselli, Cristina Bergnach, Fiorenza Orlando, Carmela Silvestri, Federico Mocchegiani, Alberto Licci, Barbara Skerlavaj, Marco Rocchi, Vittorio Saba, Margherita Zanetti, Giorgio Scalise |
Journal | Antimicrobial agents and chemotherapy
(Antimicrob Agents Chemother)
Vol. 50
Issue 5
Pg. 1672-9
(May 2006)
ISSN: 0066-4804 [Print] United States |
PMID | 16641434
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Bacterial Agents
- Antimicrobial Cationic Peptides
- Endotoxins
- Nitrites
- Tumor Necrosis Factor-alpha
- Imipenem
- Polymyxin B
- Piperacillin
- Cathelicidins
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Topics |
- Animals
- Anti-Bacterial Agents
(administration & dosage, therapeutic use)
- Antimicrobial Cationic Peptides
(pharmacology, therapeutic use)
- Cecum
(microbiology)
- Disease Models, Animal
- Endotoxins
(blood)
- Escherichia coli
(classification, drug effects)
- Escherichia coli Infections
(drug therapy, microbiology)
- Gram-Negative Bacteria
(classification, drug effects)
- Imipenem
(administration & dosage)
- Injections, Intraperitoneal
- Male
- Nitrites
(metabolism)
- Piperacillin
(administration & dosage)
- Polymyxin B
(administration & dosage)
- Random Allocation
- Rats
- Rats, Wistar
- Serotyping
- Shock, Septic
(drug therapy, microbiology)
- Tumor Necrosis Factor-alpha
(analysis)
- Cathelicidins
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