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Systemic inflammation alters the inflammatory response in experimental lipopolysaccharide-induced meningitis.

O'Reilly, Terence and Ostergaard, C and Vaxelaire, Juliane and Zak, O (2007) Systemic inflammation alters the inflammatory response in experimental lipopolysaccharide-induced meningitis. Clinical and Experimental Immunology, 147 (1). pp. 112-119. ISSN 0009-9104

Abstract

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 O111:B4 lipopolysacharide (LPS) intravenously at various doses (1, 3 or 10 microg) 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/microl) at 4 h post-injection. Blood leucocytes were slightly elevated (12 000 +/- 500/microl at 0 h; 16 900 +/- 280/microl at 8 h) but plasma TNF was always undetectable (< 0.05 ng/ml). Conversely, intravenous injection of 3 or 10 microg LPS 2 h prior to intracisternal LPS injection impaired pleocytosis (peak < 220 cells/microl) and delayed ( approximately 4 h) and reduced peak CSF TNF levels (3 microg LPS 5.0 +/- 1.2 ng/ml; 10 microg LPS 6.9 +/- 1.9; P < 0.05). Intravenous administration of 1 microg LPS was less inhibitory to CSF inflammation, but delayed onset (peak 1100 +/- 60 leucocytes/microl CSF at 8 h; 6.3 +/- 0.3 ng TNF/ml CSF at 4 h; both P < 0.05). Neutropenia nadirs were dependent on LPS dose (1 microg, 4500 +/- 1700; 3 microg, 1900 +/- 60; 10 microg, 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.

Item Type: Article
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Additional Information: free final full text version available at PubMedCentral; archiving not allowed on institutional repository
Keywords: endotoxaemia; inflammation; leucocytes; lipopolysaccharide; meningitis
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Date Deposited: 14 Dec 2009 13:58
Last Modified: 31 Jan 2013 01:13
URI: https://oak.novartis.com/id/eprint/552

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