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Abstract：
In this work, we propose a dynamical systems perspective on the modeling of sepsis and its organ-damaging consequences. We develop a functional two-layer network model for sepsis based upon the interaction of parenchymal cells and immune cells via cytokines, and the coevolutionary dynamics of parenchymal, immune cells, and cytokines. By means of the simple paradigmatic model of phase oscillators in a two-layer system, we analyze the emergence of organ threatening interactions between the dysregulated immune system and the parenchyma. We demonstrate that the complex cellular cooperation between parenchyma and stroma (immune layer) either in the physiological or in the pathological case can be related to dynamical patterns of the network. In this way we explain sepsis by the dysregulation of the healthy homeostatic state (frequency synchronized) leading to a pathological state (desynchronized or multifrequency cluster) in the parenchyma. We provide insight into the complex stabilizing and destabilizing interplay of parenchyma and stroma by determining critical interaction parameters. The coupled dynamics of parenchymal cells (metabolism) and nonspecific immune cells (response of the innate immune system) is represented by nodes of a duplex layer. Cytokine interaction is modeled by adaptive coupling weights between nodes representing immune cells (with fast adaptation timescale) and parenchymal cells (slow adaptation timescale), and between pairs of parenchymal and immune cells in the duplex network (fixed bidirectional coupling). The proposed model allows for a functional description of organ dysfunction in sepsis and the recurrence risk in a plausible pathophysiological context.
摘要：
在这项工作中,我们提出了一个关于脓毒症及其器官损害后果建模的动力系统观点。我们基于实质细胞和免疫细胞通过细胞因子的相互作用，开发了脓毒症的功能性两层网络模型。和实质的共进化动力学，免疫细胞，和细胞因子。通过两层系统中相位振荡器的简单范式模型，我们分析了免疫系统失调和实质之间的器官威胁相互作用的出现。我们证明，在生理或病理情况下，薄壁组织和基质（免疫层）之间的复杂细胞合作可能与网络的动态模式有关。通过这种方式，我们通过健康体内平衡状态（频率同步）的失调来解释败血症，从而导致实质中的病理状态（去同步或多频率簇）。通过确定关键的相互作用参数，我们可以深入了解薄壁组织和基质的复杂稳定和不稳定相互作用。实质细胞（代谢）和非特异性免疫细胞（先天免疫系统的反应）的耦合动力学由双链层的节点表示。细胞因子相互作用通过代表免疫细胞（具有快速适应时间尺度）和实质细胞（缓慢适应时间尺度）的节点之间的自适应耦合权重来建模。以及双链网络中的实质和免疫细胞对之间（固定双向耦合）。所提出的模型可以对败血症中的器官功能障碍进行功能描述，并在合理的病理生理背景下对复发风险进行描述。
