title: Potential therapeutic role of cationic peptides in three experimental models of septic shock.
abstract: The therapeutic efficacies of buforin II, indolicidin, and KFFKFFKFF were investigated in three rat models of septic shock: (i) rats injected intraperitoneally with 10 microg of Escherichia coli O111:B4 lipopolysaccharide, (ii) rats given an intraperitoneal injection of 2 x 10(10) 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-alpha) concentrations in plasma, and lethality. Treatment with all peptides resulted in significant reductions in plasma endotoxin and TNF-alpha 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.
authors.affiliation: Institute of Infectious Diseases and Public Health, University of Ancona, Ancona, Italy. anconacmi@interfree.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Giacometti
authors.forename: Oscar
authors.initials: O
authors.lastname: Cirioni
authors.forename: Roberto
authors.initials: R
authors.lastname: Ghiselli
authors.forename: Federico
authors.initials: F
authors.lastname: Mocchegiani
authors.forename: Maria Simona
authors.initials: MS
authors.lastname: Del Prete
authors.forename: Claudio
authors.initials: C
authors.lastname: Viticchi
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kamysz
authors.forename: Elzbieta
authors.initials: E
authors.lastname: ŁEmpicka
authors.forename: Vittorio
authors.initials: V
authors.lastname: Saba
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scalise
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood; D008297:Male; D008826:Microbial Sensitivity Tests; D011506:Proteins / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D004731:Endotoxins; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; C097849:buforin II; C073143:indolicidin