Integrated Inflammatory Stress (ITIS) Model
Integrated Inflammatory Stress (ITIS) Model
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DOI：
10.1007/s11538-017-0293-2
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发表时间：
2017-07-01
影响因子：
3.5
通讯作者：
Ottesen, Johnny T.
中科院分区：
文献类型：
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作者：
Bangsgaard, Elisabeth O.;Hjorth, Poul G.;Ottesen, Johnny T.
在过去的十年中，急性炎症反应和下丘脑-肾上腺-肾上腺（HPA）轴之间的耦合越来越受到关注。炎症反应被病原体或损伤相关的分子模式急性激活，而HPA轴保持长期水平的应激激素皮质醇，这也是抗炎的。提出了一个新的炎症系统的这两个子系统之间的相互作用的集成模型，并创造了集成炎症应激（ITIS）模型。基于生物推理及其描述临床数据的能力，制定了描述ITIS模型中子系统之间相互作用的耦合机制。ITIS模型通过模拟与内毒素（LPS）暴露相关的各种场景进行校准和验证。该模型能够再现肿瘤坏死因子α、促肾上腺皮质激素（ACTH）和皮质醇的人体数据，并表明重复注射LPS导致反应不足。ITIS模型预测，在一天的早些时候观察到ACTH和皮质醇浓度对LPS注射的最广泛的反应。恒定激活导致模型中变量水平升高，而ACTH和皮质醇浓度振荡的长期变化是模型预测的不同LPS剂量的最显著结果。
During the last decade, there has been an increasing interest in the coupling between the acute inflammatory response and the Hypothalamic-Pituitary-Adrenal (HPA) axis. The inflammatory response is activated acutely by pathogen- or damage-related molecular patterns, whereas the HPA axis maintains a long-term level of the stress hormone cortisol which is also anti-inflammatory. A new integrated model of the interaction between these two subsystems of the inflammatory system is proposed and coined the integrated inflammatory stress (ITIS) model. The coupling mechanisms describing the interactions between the subsystems in the ITIS model are formulated based on biological reasoning and its ability to describe clinical data. The ITIS model is calibrated and validated by simulating various scenarios related to endotoxin (LPS) exposure. The model is capable of reproducing human data of tumor necrosis factor alpha, adrenocorticotropic hormone (ACTH) and cortisol and suggests that repeated LPS injections lead to a deficient response. The ITIS model predicts that the most extensive response to an LPS injection in ACTH and cortisol concentrations is observed in the early hours of the day. A constant activation results in elevated levels of the variables in the model while a prolonged change of the oscillations in ACTH and cortisol concentrations is the most pronounced result of different LPS doses predicted by the model.