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脓毒性休克早期促炎和抗炎细胞因子的动力学建模

Dynamical modeling of pro- and anti-inflammatory cytokines in the early stage of septic shock.

作者信息

Tallon J, Browning B, Couenne F, Bordes C, Venet F, Nony P, Gueyffier F, Moucadel V, Monneret G, Tayakout-Fayolle M

机构信息

Université Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007, Villeurbanne, France.

Hospices Civils de Lyon, LYON Cedex 03 - France.

出版信息

In Silico Biol. 2020;14(1-2):101-121. doi: 10.3233/ISB-200474.

Abstract

A dynamical model of the pathophysiological behaviors of IL18 and IL10 cytokines with their receptors is tested against data for the case of early sepsis. The proposed approach considers the surroundings (organs and bone marrow) and the different subsystems (cells and cyctokines). The interactions between blood cells, cytokines and the surroundings are described via mass balances. Cytokines are adsorbed onto associated receptors at the cell surface. The adsorption is described by the Langmuir model and gives rise to the production of more cytokines and associated receptors inside the cell. The quantities of pro and anti-inflammatory cytokines present in the body are combined to give global information via an inflammation level function which describes the patient's state. Data for parameter estimation comes from the Sepsis 48 H database. Comparisons between patient data and simulations are presented and are in good agreement. For the IL18/IL10 cytokine pair, 5 key parameters have been found. They are linked to pro-inflammatory IL18 cytokine and show that the early sepsis is driven by components of inflammatory character.

摘要

针对早期脓毒症病例的数据,测试了一种包含白细胞介素18(IL18)和白细胞介素10(IL10)细胞因子及其受体病理生理行为的动力学模型。所提出的方法考虑了周围环境(器官和骨髓)以及不同的子系统(细胞和细胞因子)。血细胞、细胞因子与周围环境之间的相互作用通过质量平衡来描述。细胞因子吸附在细胞表面的相关受体上。吸附作用由朗缪尔模型描述,并导致细胞内产生更多的细胞因子和相关受体。体内促炎和抗炎细胞因子的数量通过一个描述患者状态的炎症水平函数进行综合,以提供全局信息。参数估计的数据来自脓毒症48小时数据库。给出了患者数据与模拟结果的比较,二者吻合良好。对于IL18/IL10细胞因子对,已发现5个关键参数。它们与促炎IL18细胞因子相关,表明早期脓毒症是由具有炎症特征的成分驱动的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2c4/7505012/ca9acf820502/isb-13-isb200474-g001.jpg

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