Day Judy, Rubin Jonathan, Vodovotz Yoram, Chow Carson C, Reynolds Angela, Clermont Gilles
Department of Mathematics, 301 Thackeray, University of Pittsburgh, Pittsburgh, PA 15260, USA.
J Theor Biol. 2006 Sep 7;242(1):237-56. doi: 10.1016/j.jtbi.2006.02.015. Epub 2006 Apr 17.
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.
细菌脂多糖（LPS；内毒素）是一种强效免疫刺激剂，可引发类似于细菌感染的急性炎症反应。实验观察表明，重复给予内毒素可使这种生物学反应减弱（耐受）或增强（增效）。这两种现象都具有临床相关性。我们表明，这种反应的四维微分方程模型再现了许多涉及重复给予内毒素的情况。特别是，在不同的给药方案下，该模型可以从单个参数集显示耐受和增效。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。这些发现支持了以下假设：内毒素耐受和其他相关现象可被视为统一急性炎症反应的动态表现，并提供了与对内毒素这种反应动力学相关的具体预测。
