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.