A reduced mathematical model of the acute inflammatory response II. Capturing scenarios of repeated endotoxin administration
A reduced mathematical model of the acute inflammatory response II. Capturing scenarios of repeated endotoxin administration
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DOI：
10.1016/j.jtbi.2006.02.015
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发表时间：
2006-09-07
影响因子：
2
通讯作者：
Clermont, Gilles
中科院分区：
文献类型：
--
作者：
Day, Judy;Rubin, Jonathan;Clermont, Gilles
细菌脂多糖(内毒素)是一种有效的免疫刺激剂，可引起与细菌感染相当的急性炎症反应。实验观察表明，反复给予内毒素可以钝化(耐受)或增强(增强)这种生物学反应。这两种现象都与临床相关。我们表明，这一反应的四维微分方程模型再现了许多涉及重复内毒素注射的场景。具体地说，该模型可以在不同的给药场景下显示单个参数集的容差和增强。我们模拟结果的关键决定因素是模型组件的相对时间尺度。这些发现支持这样的假设，即内毒素耐受和其他相关现象可以被认为是统一的急性炎症反应的动态表现，并提供了与内毒素反应动力学相关的特定预测。(C)2006爱思唯尔有限公司。保留所有权利。
Bacterial lipopolysaccharide (LPS; endotoxin) is a potent immunostimulant that can induce an acute inflammatory response comparable to a bacterial infection. Experimental observations demonstrate that this biological response can be either blunted (tolerance) or augmented (potentiation) with repeated administration of endotoxin. Both phenomena are of clinical relevance. We show that a four-dimensional differential equation model of this response reproduces many scenarios involving repeated endotoxin administration. In particular, the model can display both tolerance and potentiation from a single parameter set, under different administration scenarios. The key determinants of the outcome of our simulations are the relative time-scales of model components. These findings support the hypothesis that endotoxin tolerance and other related phenomena can be considered as dynamic manifestations of a unified acute inflammatory response, and offer specific predictions related to the dynamics of this response to endotoxin. (c) 2006 Elsevier Ltd. All rights reserved.