Systemic inflammation alters the inflammatory response in experimental lipopolysaccharide-induced meningitis
Systemic inflammation alters the inflammatory response in experimental lipopolysaccharide-induced meningitis
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DOI：
10.1111/j.1365-2249.2006.03255.x
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发表时间：
2007-01-01
影响因子：
4.6
通讯作者：
Zak, O.
中科院分区：
文献类型：
--
作者：
O'Reilly, T.;Ostergaard, C.;Zak, O.
为了确定全身性炎症是否改变脑膜炎，进行了评价内毒素血症水平和持续时间对脑膜炎性反应的影响的实验。在脑池内注射前，家兔静脉内接受不同剂量（1、3或10 μ g）和时间（-8、-2或0 h）的生理盐水或大肠杆菌0111：134脂多糖（LPS）。注射20 ng LPS。脑池内注射LPS与盐水一起静脉注射在注射后2小时产生峰值脑脊液（CSF）肿瘤坏死因子（TNF）水平（95 +/- 26 ng/ml），在注射后4小时产生峰值白细胞水平（5413 +/- 764个细胞/μ l）。血液白细胞轻微升高（0 h时为12 000 +/- 500/mu l; 8 h时为16 900 +/- 280/mu l），但血浆TNF始终检测不到（< 0.05 ng/ml）。相反，在脑池内注射LPS前2小时静脉注射3或10 μ g LPS损害了白细胞增多（峰值< 220个细胞/μ l），延迟（类似于4小时）并降低了CSF TNF峰值水平（3 μ g LPS 5.0 +/- 1.2 ng/ml; 10 μ g LPS 6.9 +/- 1.9; P < 0.05）。静脉注射1 μ g LPS对CSF炎症的抑制作用较小，但延迟了发病（8小时时达到峰值1100 +/-60个白细胞/μ l CSF; 4小时时达到峰值6.3 +/-0.3 μ g TNF/ml CSF;两者均P < 0.05）。中性粒细胞最低点依赖于LPS剂量（1 μ g，4500 +/- 1700; 3 μ g，1900 +/- 60; 10 μ g，1100 +/- 100，均在静脉内给药后4小时）。血浆TNF峰值水平无剂量依赖性（> 8 ng/ml），但血浆TNF总是可检测到（静脉给药后10 h> 0.2 ng/ml）。0 h静脉注射LPS也能阻断细胞增殖，但~ 8 h注射LPS后抑制作用消失。总之，内毒素血症的程度和持续时间影响实验性脑膜炎对LPS的脑膜炎性反应。
Experiments to evaluate the effect of the level and duration of endotoxaemia on the meningeal inflammatory response were performed in order to determine if systemic inflammation alters meningitis. Rabbits received either saline or Escherichia coli 0111:134 lipopolysacharide (LPS) intravenously at various doses (1, 3 or 10 mu g) and times (-8, -2 or 0 h) before an intracisternal. injection of 20 ng LPS. An intracisternal LPS injection together with saline intravenously produced a peak cerebrospinal fluid (CSF) tumour necrosis factor (TNF) level (95 +/- 26 ng/ml) at 2 h and peak leucocyte level (5413 +/- 764 cells/mu l) at 4 h post-injection. Blood leucocytes were slightly elevated (12 000 +/- 500/mu l at 0 h; 16 900 +/- 280/mu l at 8 h) but plasma TNF was always undetectable (< 0.05 ng/ml). Conversely, intravenous injection of 3 or 10 mu g LPS 2 h prior to intracisternal LPS injection impaired pleocytosis (peak < 220 cells/mu l) and delayed (similar to 4 h) and reduced peak CSF TNF levels (3 mu g LPS 5.0 +/- 1.2 ng/ml; 10 mu g LPS 6.9 +/- 1.9; P < 0.05). Intravenous administration of 1 mu g LPS was less inhibitory to CSF inflammation, but delayed onset (peak 1100 +/- 60 leucocytes/mu l CSF at 8 h; 6.3 +/- 0.3 mu g TNF/ml CSF at 4 h; both P < 0.05). Neutropenia nadirs were dependent on LPS dose (1 mu g, 4500 +/- 1700; 3 mu g, 1900 +/- 60; 10 mu g, 1100 +/- 100 all at 4 h post-intravenous dose). Peak plasma TNF levels were not dose-dependent (> 8 ng/ml), but plasma TNF was always detectable (> 0.2 ng/ml at 10 h post-intravenous dose). Intravenous LPS administration at 0 h also blocked pleocytosis, but the inhibitory effect was lost when administration at -8 h. In conclusion, the degree and duration of endotoxaemia affect the meningeal inflammatory response to LPS in experimental meningitis.