Ammons W S, Kohn F R, Kung A H
Department of Pharmacology and Toxicology, XOMA Corp., Berkeley, California.
J Infect Dis. 1994 Dec;170(6):1473-82. doi: 10.1093/infdis/170.6.1473.
Effects of an N-terminal fragment of bactericidal/permeability increasing protein (rBPI21) on bacterial infections were determined. Intravenous (i.v.) rBPI21 increased survival and reduced bacteremia in rats after an iv injection of Escherichia coli O7:K1 bacteria. rBPI21 inhibited the rise in tumor necrosis factor-alpha resulting from challenge with 2 strains of E. coli. Intraperitoneal (ip) injection of rBPI21 increased survival of mice after ip injection of E. coli O7:K1 and Pseudomonas aeruginosa and reduced bacteria in peritoneal lavage fluid and blood and inhibited cytokine production in response to E. coli. rBPI21 alone did not protect mice challenged with E. coli O111:B4 but was protective and reduced bacterial counts when administered in combination with the antibiotic cefamandole. The data show that protection with rBPI21 is associated with reductions in bacterial counts and is enhanced by antibiotics. Bactericidal activity, in addition to antiendotoxin activity, is involved in the efficacy of rBPI21 in models of gram-negative infection.
测定了杀菌/通透性增加蛋白（rBPI21）的N端片段对细菌感染的影响。静脉注射（i.v.）rBPI21可提高大鼠静脉注射大肠杆菌O7:K1细菌后的存活率并减少菌血症。rBPI21可抑制两株大肠杆菌攻击后肿瘤坏死因子-α的升高。腹腔注射（ip）rBPI21可提高小鼠腹腔注射大肠杆菌O7:K1和铜绿假单胞菌后的存活率，并减少腹腔灌洗液和血液中的细菌数量，同时抑制对大肠杆菌产生的细胞因子。单独使用rBPI21不能保护受到大肠杆菌O111:B4攻击的小鼠，但与抗生素头孢孟多联合使用时具有保护作用并减少细菌数量。数据表明，rBPI21的保护作用与细菌数量减少有关，且抗生素可增强这种作用。除抗内毒素活性外，杀菌活性也参与了rBPI21在革兰氏阴性感染模型中的疗效。
