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

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/±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. © 1995, by The University of Chicago.