Baldwin G, Alpert G, Caputo G L, Baskin M, Parsonnet J, Gillis Z A, Thompson C, Siber G R, Fleisher G R
Department of Medicine, Children's Hospital, Boston, MA 02115.
J Infect Dis. 1991 Sep;164(3):542-9. doi: 10.1093/infdis/164.3.542.
Meningococcemia is the most frequent cause of septic shock in healthy children. To determine whether polymyxin B (PMB) might improve mortality from meningococcal shock, its protective activity was evaluated in rabbits challenged with an LD90 of meningococcal lipooligosaccharide (LOS) and compared with an LD80 of Escherichia coli O111:B4 lipopolysaccharide (LPS). PMB (5 mg/kg) administered intravenously 30 min before meningococcal LOS challenge had no significant effect on heart rate, mean arterial pressure, serum bicarbonate, serum tumor necrosis factor (TNF) levels, or survival relative to controls. However, PMB premixed with LOS in vitro increased serum bicarbonate levels (P less than .05) and improved 24-h survival (P less than .05). In contrast, PMB given before E. coli LPS challenge increased serum bicarbonate levels, decreased TNF levels, and improved 24-h survival (all, P less than .05). In vitro studies confirmed that PMB at 10 micrograms/ml neutralized E. coli LPS but not meningococcal LOS activity. Thus, pretreatment with PMB apparently protects rabbits against shock induced by E. coli LPS but not by meningococcal LOS.
脑膜炎球菌血症是健康儿童感染性休克最常见的病因。为了确定多粘菌素B（PMB）是否能降低脑膜炎球菌性休克的死亡率，研究人员在受到脑膜炎球菌脂寡糖（LOS）半数致死剂量（LD90）攻击的兔子身上评估了其保护活性，并与大肠杆菌O111:B4脂多糖（LPS）的LD80进行了比较。在脑膜炎球菌LOS攻击前30分钟静脉注射PMB（5毫克/千克），相对于对照组，对心率、平均动脉压、血清碳酸氢盐、血清肿瘤坏死因子（TNF）水平或生存率没有显著影响。然而，体外将PMB与LOS预混合可提高血清碳酸氢盐水平（P<0.05）并改善24小时生存率（P<0.05）。相比之下，在大肠杆菌LPS攻击前给予PMB可提高血清碳酸氢盐水平，降低TNF水平，并改善24小时生存率（所有P<0.05）。体外研究证实，10微克/毫升的PMB可中和大肠杆菌LPS，但不能中和脑膜炎球菌LOS的活性。因此，PMB预处理显然能保护兔子免受大肠杆菌LPS诱导的休克，但不能保护其免受脑膜炎球菌LOS诱导的休克。
