Kartalija M, Kim Y, White M L, Nau R, Tureen J H, Täuber M G
Infectious Diseases Laboratory, San Francisco General Hospital, California.
J Infect Dis. 1995 Apr;171(4):948-53. doi: 10.1093/infdis/171.4.948.
Endotoxin triggers the subarachnoid inflammation of gram-negative meningitis. This study examined the ability of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein (rBPI23) to block endotoxin-induced meningitis in rabbits. Intracisternal (ic) injection of 10-20 ng of meningococcal endotoxin induced high cerebrospinal fluid (CSF) concentrations of tumor necrosis factor (TNF) and CSF pleocytosis and increased CSF lactate concentrations. ic administration of rBPI23 significantly reduced meningococcal endotoxin-induced TNF release into CSF (P < .005), lactate concentrations (P < .001), and CSF white blood cell counts (P < .01). No such effect was observed in animals receiving intravenous rBPI23. Concentrations of rBPI23 in CSF were high after ic administration but low or undetectable after systemic administration. Thus, high concentrations of rBPI23 can effectively neutralize meningococcal endotoxin in CSF, but low CSF concentrations after systemic administration currently limit its potential usefulness as adjunctive drug treatment in gram-negative meningitis.
内毒素引发革兰氏阴性菌脑膜炎的蛛网膜下腔炎症。本研究检测了杀菌/通透性增加蛋白重组N端片段（rBPI23）阻断家兔内毒素诱导性脑膜炎的能力。脑池内（ic）注射10 - 20 ng脑膜炎球菌内毒素可诱导脑脊液（CSF）中肿瘤坏死因子（TNF）浓度升高、CSF细胞增多以及CSF乳酸盐浓度升高。脑池内给予rBPI23可显著降低脑膜炎球菌内毒素诱导的TNF释放至CSF中的量（P <.005）、乳酸盐浓度（P <.001）以及CSF白细胞计数（P <.01）。在静脉给予rBPI23的动物中未观察到此类效应。脑池内给药后CSF中rBPI23浓度较高，但全身给药后浓度较低或无法检测到。因此，高浓度的rBPI23可有效中和CSF中的脑膜炎球菌内毒素，但目前全身给药后CSF中低浓度限制了其作为革兰氏阴性菌脑膜炎辅助药物治疗的潜在用途。
