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/permeability-increasing protein (rBPI(23)), on cytokine release and neutrophil activation in endotoxemia in humans, 8 volunteers were challenged twice with endotoxin and concurrently received either rBPI(23) or placebo in a randomized, placebo controlled, double-blind crossover study. rBPI(23) 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 rBPI(23). The results of this study indicate that rBPI(23) is capable of neutralizing many of the biologic effects of endotoxin in humans.