Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/permeability-increasing protein

J Infect Dis. 1995 Jul;172(1):144-51. doi: 10.1093/infdis/172.1.144.

Abstract

To investigate the effects of a recombinant endotoxin-binding protein, bactericidal/permeability-increasing protein (rBPI23), on cytokine release and neutrophil activation in endotoxemia in humans, 8 volunteers were challenged twice with endotoxin and concurrently received either rBPI23 or placebo in a randomized, placebo controlled, double-blind crossover study, rBPI23 treatment significantly lowered circulating endotoxin levels (P = .02) and resulted in a significant reduction in the release of tumor necrosis factor (TNF), soluble TNF receptors p55 and p75, interleukin (IL)-6, IL-8 (P < .01 for each), and IL-10 levels (P = .02) but did not prevent the endotoxin-induced rise in body temperature. The early endotoxin-induced leukopenia was blunted (P = .08), and neutrophil degranulation, as measured by circulating levels of elastase/alpha 1-antitrypsin complexes (P = .03) and lactoferrin (P < .01), was largely prevented by rBPI23. The results of this study indicate that rBPI23 is capable of neutralizing many of the biologic effects of endotoxin in humans.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimicrobial Cationic Peptides
  • Blood Bactericidal Activity
  • Blood Cell Count / drug effects
  • Blood Proteins / pharmacokinetics
  • Blood Proteins / pharmacology*
  • Body Temperature / drug effects
  • Cross-Over Studies
  • Cytokines / biosynthesis*
  • Cytokines / blood
  • Double-Blind Method
  • Endotoxins / pharmacology*
  • Endotoxins / toxicity
  • Escherichia coli
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Interleukin-8 / biosynthesis
  • Leukocyte Count / drug effects
  • Lipopolysaccharides / pharmacology*
  • Lipopolysaccharides / toxicity
  • Male
  • Membrane Proteins*
  • Metabolic Clearance Rate
  • Neutrophils / drug effects
  • Neutrophils / physiology*
  • Placebos
  • Receptors, Tumor Necrosis Factor / biosynthesis
  • Recombinant Proteins / pharmacokinetics
  • Recombinant Proteins / pharmacology
  • Time Factors
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Antimicrobial Cationic Peptides
  • Blood Proteins
  • Cytokines
  • Endotoxins
  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharides
  • Membrane Proteins
  • Placebos
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • bactericidal permeability increasing protein
  • Interleukin-10