A comparison of bactericidal/permeability-increasing protein variant versus recombinant endotoxin-neutralizing protein for the treatment of Escherichia coli sepsis in rats .

OBJECTIVE

To compare a recombinant bactericidal/permeability-increasing protein variant and a recombinant endotoxin-neutralizing protein.

DESIGN

Randomized, blinded, controlled study, using a rat model of sepsis.

SETTING

Animal research facility.

SUBJECTS

Male Wistar rats.

INTERVENTIONS

An inoculum of 1.5 x 10(7) to 1.8 x 10(8) Escherichia coli O18ac K1, implanted in the peritoneum, produced bacteremia in 95% of animals after 1 hr. One hour after E. coli challenge, animals received recombinant bactericidal/permeability-increasing protein variant, recombinant endotoxin-neutralizing protein, or saline intravenously, followed by ceftriaxone and gentamicin intramuscularly.

MEASUREMENTS AND MAIN RESULTS

Twenty-four (85.7%) of 28 animals receiving recombinant endotoxin-neutralizing protein (p < .001 vs. control) survived 7 days compared with nine (33.3%) of 27 recombinant bactericidal/permeability-increasing protein variant-treated (p < .001 vs. control) and two (6.5%) of 31 control animals.

CONCLUSIONS

Both recombinant endotoxin-neutralizing protein and recombinant bactericidal/permeability-increasing protein variant improved survival. Recombinant endotoxin-neutralizing protein was superior to recombinant bactericidal/permeability-increasing protein variant in its protective effect at the doses tested. Our results suggest that both proteins may be useful in the treatment of human Gram-negative sepsis.