Inhibition of Endotoxin-Induced Cytokine Release and Neutrophil Activation in Humans by Use of Recombinant Bactericidal/Permeability-Increasing Protein

• Published in: The Journal of infectious diseases 1995-07, Vol.172 (1), p.144-151
• Main Authors: von der Möhlen, Marijke A. M., Kimmings, A. Nikola, Wedel, Nancy I., Mevissen, Marcel L. C. M., Jansen, Jaap, Friedmann, Nadav, Lorenz, Todd J., Nelson, Betty J., White, Mark L., Bauer, Robert, Hack, C. Erik, Eerenberg, Anke J. M., van Deventer, Sander J. H.
• Format: Article
• Language: English
• Subjects: Antimicrobial Cationic Peptides; Biological and medical sciences; Blood; Blood Bactericidal Activity; Blood Cell Count - drug effects; Blood plasma; Blood Proteins - pharmacokinetics; Blood Proteins - pharmacology; Body Temperature - drug effects; Cardiovascular system; Cross-Over Studies; Cytokines; Cytokines - biosynthesis; Cytokines - blood; Double-Blind Method; Endotoxins; Endotoxins - pharmacology; Endotoxins - toxicity; Escherichia coli; Health care administration; Humans; Interleukin-10 - biosynthesis; Interleukin-6 - biosynthesis; Interleukin-8 - biosynthesis; Leukocyte Count - drug effects; Leukocytes; Lipopolysaccharides - pharmacology; Lipopolysaccharides - toxicity; Major Articles; Male; Medical sciences; Membrane Proteins; Metabolic Clearance Rate; Miscellaneous; Neutrophils; Neutrophils - drug effects; Neutrophils - physiology; Pharmacology. Drug treatments; Placebos; Proteins; Receptors, Tumor Necrosis Factor - biosynthesis; Recombinant Proteins - pharmacokinetics; Recombinant Proteins - pharmacology; Time Factors; Tumor Necrosis Factor-alpha - biosynthesis; Tumor necrosis factors
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/172.1.144

To investigate the effects of a recombinant endotoxin-binding protein, bactericidal/permeabilityincreasing 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/α1-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.