Mavroudis Panteleimon D, Corbett Siobhan A, Calvano Steven E, Androulakis Ioannis P
Chemical & Biochemical Engineering Department, Rutgers University, Piscataway, NJ, United States.
Department of Surgery, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, United States.
Math Biosci. 2015 Feb;260:54-64. doi: 10.1016/j.mbs.2014.10.006. Epub 2014 Oct 31.
In this work we explore a semi-mechanistic model that considers cortisol's permissive and suppressive effects through the regulation of cytokine receptors and cytokines respectively. Our model reveals the proactive role of cortisol during the resting period and its reactive character during the body's activity phase. Administration of an acute LPS dose during the night, when cortisol's permissive effects are higher than suppressive, leads to increased cytokine levels compared to LPS administration at morning when cortisol's suppressive effects are higher. Interestingly, our model presents a hysteretic behavior where the relative predominance of permissive or suppressive effects results not only from cortisol levels but also from the previous states of the model. Therefore, for the same cortisol levels, administration of an inflammatory stimulus at cortisol's ascending phase, that follows a time period where cytokine receptor expression is elevated ultimately sensitizing the body for the impending stimulus, leads to higher cytokine expression compared to administration of the same stimulus at cortisol's descending phase.
在这项工作中，我们探索了一种半机械模型，该模型分别通过细胞因子受体和细胞因子的调节来考虑皮质醇的允许和抑制作用。我们的模型揭示了皮质醇在静息期的积极作用及其在身体活动阶段的反应特性。与早晨给予脂多糖（LPS）相比，夜间给予急性剂量的LPS时，皮质醇的允许作用高于抑制作用，导致细胞因子水平升高，而早晨皮质醇的抑制作用更强。有趣的是，我们的模型呈现出一种滞后行为，其中允许或抑制作用的相对优势不仅取决于皮质醇水平，还取决于模型的先前状态。因此，对于相同的皮质醇水平，在皮质醇上升阶段给予炎症刺激，即在细胞因子受体表达升高的时间段之后，最终使身体对即将到来的刺激敏感，与在皮质醇下降阶段给予相同刺激相比，会导致更高的细胞因子表达。
