This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cirioni, O.
Right arrow Articles by Scalise, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cirioni, O.
Right arrow Articles by Scalise, G.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2006, p. 1672-1679, Vol. 50, No. 5
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.5.1672-1679.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

LL-37 Protects Rats against Lethal Sepsis Caused by Gram-Negative Bacteria

Oscar Cirioni,1 Andrea Giacometti,1* Roberto Ghiselli,2 Cristina Bergnach,3 Fiorenza Orlando,4 Carmela Silvestri,1 Federico Mocchegiani,2 Alberto Licci,1 Barbara Skerlavaj,3 Marco Rocchi,5 Vittorio Saba,2 Margherita Zanetti,3,6 and Giorgio Scalise1

Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy,1 Department of General Surgery, I.N.R.C.A. I.R.R.C.S., Università Politecnica delle Marche, Ancona, Italy,2 Department of Biomedical Sciences and Technology, University of Udine, Udine, Italy,3 Experimental Animal Models for Aging Units, Research Department, I.N.R.C.A. I.R.R.C.S., Ancona, Italy,4 Institute of Biomathematics, Faculty of Pharmacy, University of Urbino, Urbino, Italy,5 National Laboratory, CIB, Area Science Park, Padriciano 99, 34012 Trieste, Italy6

Received 5 November 2005/ Returned for modification 29 November 2005/ Accepted 17 January 2006

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 1010 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.

* Corresponding author. Mailing address: Clinica Malattie Infettive, c/o Ospedale Regionale, Via Conca 71, 60020 Torrette AN, Italy. Phone: 39 071 5963715. Fax: 39 071 5963468. E-mail: anconacmi{at}interfree.it.

Antimicrobial Agents and Chemotherapy, May 2006, p. 1672-1679, Vol. 50, No. 5
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.5.1672-1679.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cirioni, O., Ghiselli, R., Silvestri, C., Kamysz, W., Orlando, F., Riva, A., Kamysz, E., Castelletti, S., Rocchi, M., Saba, V., Scalise, G., Giacometti, A. (2008). Efficacy of the Combination of Tachyplesin III and Clarithromycin in Rat Models of Escherichia coli Sepsis. Antimicrob. Agents Chemother. 52: 4351-4355 [Abstract] [Full Text]  
  • Wang, G. (2008). Structures of Human Host Defense Cathelicidin LL-37 and Its Smallest Antimicrobial Peptide KR-12 in Lipid Micelles. J. Biol. Chem. 283: 32637-32643 [Abstract] [Full Text]  
  • Tomasinsig, L., Pizzirani, C., Skerlavaj, B., Pellegatti, P., Gulinelli, S., Tossi, A., Virgilio, F. D., Zanetti, M. (2008). The Human Cathelicidin LL-37 Modulates the Activities of the P2X7 Receptor in a Structure-dependent Manner. J. Biol. Chem. 283: 30471-30481 [Abstract] [Full Text]  
  • Lisanby, M. W., Swiecki, M. K., Dizon, B. L. P., Pflughoeft, K. J., Koehler, T. M., Kearney, J. F. (2008). Cathelicidin Administration Protects Mice from Bacillus anthracis Spore Challenge. J. Immunol. 181: 4989-5000 [Abstract] [Full Text]  
  • Harder, J., Glaser, R., Schroder, J.-M. (2007). Review: Human antimicrobial proteins effectors of innate immunity. Innate Immunity 13: 317-338 [Abstract]  
  • Kindrachuk, J., Paur, N., Reiman, C., Scruten, E., Napper, S. (2007). The PhoQ-Activating Potential of Antimicrobial Peptides Contributes to Antimicrobial Efficacy and Is Predictive of the Induction of Bacterial Resistance. Antimicrob. Agents Chemother. 51: 4374-4381 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»