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Antimicrobial Agents and Chemotherapy, July 2002, p. 2132-2136, Vol. 46, No. 7
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.7.2132-2136.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Potential Therapeutic Role of Cationic Peptides in Three Experimental Models of Septic Shock

Andrea Giacometti,^1* Oscar Cirioni,¹ Roberto Ghiselli,² Federico Mocchegiani,² Maria Simona Del Prete,¹ Claudio Viticchi,³ Wojciech Kamysz,⁴ Elbieta empicka,⁴ Vittorio Saba,² and Giorgio Scalise¹

Institute of Infectious Diseases and Public Health, University of Ancona,¹ Department of General Surgery,² Biotechnology Centre, Research Department, Istituto Nazionale Riposo e Cura Anziani Istituto di Ricovero e Cura a Carattere Scientifico, Ancona, Italy,³ Faculty of Chemistry, University of Gdansk, Gdansk, Poland⁴

Received 23 January 2002/ Returned for modification 7 March 2002/ Accepted 3 April 2002

The therapeutic efficacies of buforin II, indolicidin, and KFFKFFKFF were investigated in three rat models of septic shock: (i) rats injected intraperitoneally with 10 µg of Escherichia coli O111:B4 lipopolysaccharide, (ii) rats given an intraperitoneal injection of 2 x 10¹⁰ CFU of Escherichia coli ATCC 25922, and (iii) rats in which intra-abdominal sepsis was induced via cecal ligation and single puncture. All animals were randomized to receive parenterally isotonic sodium chloride solution, 1 mg of buforin II per kg of body weight, 1 mg of indolicidin per kg, 1 mg of KFFKFFKFF per kg, and 20 mg of imipenem per kg. The main outcome measures were bacterial growth in abdominal exudate and plasma, endotoxin and tumor necrosis factor alpha (TNF-) concentrations in plasma, and lethality. Treatment with all peptides resulted in significant reductions in plasma endotoxin and TNF- concentrations compared with those resulting from the imipenem and saline treatments. On the other hand, imipenem treatment significantly reduced the levels of bacterial growth compared with the reductions achieved with the peptide and saline treatments. All compounds reduced the rates of death compared to that for the controls. Although the peptides demonstrated lower levels of antimicrobial activity than imipenem, they exhibited the dual properties of antimicrobial and antiendotoxin agents.

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