Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/permeability-increasing protein
Autor: | M. A. M. von der Mohlen, A. N. Kimmings, N. I. Wedel, M. L. C. M. Mevissen, J. Jansen, N. Friedmann, T. J. Lorenz, B. J. Nelson, M. L. White, R. Bauer, C. E. Hack, A. J. M. Eerenberg, S. J. H. van Deventer |
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Rok vydání: | 1995 |
Předmět: |
Lipopolysaccharides
Male medicine.medical_specialty Blood Bactericidal Activity Time Factors Metabolic Clearance Rate Neutrophils medicine.medical_treatment Receptors Tumor Necrosis Factor Body Temperature Placebos Leukocyte Count Double-Blind Method Internal medicine medicine Escherichia coli Immunology and Allergy Humans Interleukin 8 Cross-Over Studies biology Interleukin-6 Tumor Necrosis Factor-alpha Elastase Interleukin-8 Interleukin Membrane Proteins Blood Proteins Bactericidal/permeability-increasing protein Recombinant Proteins Blood Cell Count Interleukin-10 Endotoxins Interleukin 10 Infectious Diseases Cytokine Endocrinology biology.protein Neutrophil degranulation Cytokines Tumor necrosis factor alpha Antimicrobial Cationic Peptides |
Zdroj: | The Journal of infectious diseases. 172(1) |
ISSN: | 0022-1899 |
Popis: | 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. |
Databáze: | OpenAIRE |
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