von der Möhlen M A, Kimmings A N, Wedel N I, Mevissen M L, Jansen J, Friedmann N, Lorenz T J, Nelson B J, White M L, Bauer R
Center for Hemostasis, Thrombosis, Atherosclerosis, and Inflammation Research, Amsterdam, Netherlands.
J Infect Dis. 1995 Jul;172(1):144-51. doi: 10.1093/infdis/172.1.144.
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.
为研究重组内毒素结合蛋白杀菌/通透性增加蛋白（rBPI23）对人类内毒素血症中细胞因子释放及中性粒细胞激活的影响，8名志愿者在一项随机、安慰剂对照、双盲交叉研究中接受两次内毒素攻击，并同时接受rBPI23或安慰剂。rBPI23治疗显著降低了循环内毒素水平（P = .02），并导致肿瘤坏死因子（TNF）、可溶性TNF受体p55和p75、白细胞介素（IL）-6、IL-8（每项P < .01）以及IL-10水平（P = .02）的释放显著减少，但未能阻止内毒素诱导的体温升高。早期内毒素诱导的白细胞减少得到缓解（P = .08），rBPI23在很大程度上阻止了中性粒细胞脱颗粒，这通过循环中弹性蛋白酶/α1-抗胰蛋白酶复合物水平（P = .03）和乳铁蛋白水平（P < .01）来衡量。本研究结果表明，rBPI23能够中和内毒素在人类中的许多生物学效应。
