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Roche, M,Diamond, M,Lonergan, I,Keeney, G,Kelly, JP,Finn, DP
The effects of acute lipopolysaccharide injection on levels of pro- and anti-inflammatory regions (vol 19, pg A37, 2005)
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cytokines brain psychoneuroimmunology depression
Administration of the bacterial endotoxin lipopolysaccharide (LPS) to rodents induces a characteristic profile of immune, neuroendocrine and behavioural alterations which models symptoms of clinical depression. Whilst the effects of LPS on peripheral cytokine levels are well characterised, knowledge of its effects on brain cytokines is limited. The aim of the present study was to investigate the effects of acute, systemic administration of LPS on levels of interleukin (IL)-1 beta, IL-6, IL-10 and interferon (IFN)-gamma in discrete rat brain regions and plasma and to establish a timecourse for these effects.Male Sprague-Dawley rats (220-260 g, n = 5-8/group) were singly housed and habituated to handling and i.p. injection for 3 days prior to receiving an acute i.p. injection of LPS (100 mu g/kg) or vehicle (0.89% sterile saline) in a volume of 1 ml/kg. Rats were killed 1, 2, 4 or 6 hr post-injection and blood taken following cardiac puncture. Brains were rapidly removed and the hippocampus, hypothalamus, cortex and amygdala were dissected out, weighed and snap frozen. Levels of IL-1 beta, IL6, IL-10 and IFN-gamma were subsequently determined directly in blood plasma and brain samples using ELISA kits (R&D Systems, Abingdon, UK). Data were analysed by one-way ANOVA followed by Student-Newman-Keuls or Bonferroni's post-hoc test.Levels of IL-1 beta were significantly elevated in the hippocampus 2, 4 and 6 hr post-LPS injection, in the cortex 4 and 6 hr post-injection, and in the hypothalamus 2 hr post-injection, compared with saline-treated controls. LPS had no significant effect on IL-1 beta levels in the amygdala. IL-10 was significantly reduced in the hypothalmus only, I hr post-LPS injection, and returned to levels comparable with saline-treated controls thereafter. LPS also induced a significant elevation in IFN-gamma in the hippocampus 6 hr post-injection. IL-6 levels remained unchanged in all brain regions and at all timepoints following LPS injection. Injection of LPS significantly elevated levels of all 4 cytokines in blood plasma with levels peaking either 2 hr (IL-1 beta, IL-6, IL-10) or 4 hr (IFN-gamma) post-injection.These data provide direct evidence for LPS-induced alterations in cytokine levels in discrete rat brain regions and establish a timecourse for these changes. The data also confirm previous studies of LPS-induced alterations in peripheral circulating cytokine levels. This work provides a basis for the design of future experiments aimed at elucidating the functional significance of these changes and their relevance to neuroimmune theories of psychiatric disorders.
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