Potential therapeutic role of cationic peptides in three experimental models of septic shock.
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.
Giacometti
Andrea
A
Institute of Infectious Diseases and Public Health, University of Ancona, Ancona, Italy. anconacmi@interfree.it
Cirioni
Oscar
O
Ghiselli
Roberto
R
Mocchegiani
Federico
F
Del Prete
Maria Simona
MS
Viticchi
Claudio
C
Kamysz
Wojciech
W
ŁEmpicka
Elzbieta
E
Saba
Vittorio
V
Scalise
Giorgio
G
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
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D004731:Endotoxins; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; C097849:buforin II; C073143:indolicidin