Inflammatory responses to an infection from a zoonotic pathogen, such as avian influenza viruses, hantaviruses and some coronaviruses, are distinctly different in their natural reservoir versus human host. While not as well studied in the natural reservoirs, the pro-inflammatory response and viral replication appear controlled and show no obvious pathology. In contrast, infection in humans results in an initial high viral load marked by an aggressive pro-inflammatory response known as a cytokine storm. The key difference in the course of the infection between the reservoir and human host is the inflammatory response. In this investigation, we apply a simple two-component differential equation model for pro-inflammatory and anti-inflammatory responses and a detailed mathematical analysis to identify specific regions in parameter space for single stable endemic equilibrium, bistability or periodic solutions. The extensions of the deterministic model to two stochastic models account for variability in responses seen at the cell (local) or tissue (global) levels. Numerical solutions of the stochastic models exhibit outcomes that are typical of a chronic infection in the natural reservoir or a cytokine storm in human infection. In the chronic infection, occasional flare-ups between high and low responses occur when model parameters are in a region of bistability or periodic solutions. The cytokine storm with a vigorous pro-inflammatory response and less vigorous anti-inflammatory response occurs in the parameter region for a single stable endemic equilibrium with a strong pro-inflammatory response. The results of the model analyses and the simulations are interpreted in terms of the functional role of the cytokines and the inflammatory responses seen in infection of the natural reservoir or of the human host.

中文翻译：

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病毒人畜共患传染病炎症反应中的细胞因子动力学模型。


人畜共患病原体（例如禽流感病毒、汉坦病毒和一些冠状病毒）感染后的炎症反应，其自然宿主与人类宿主明显不同。虽然在自然宿主中没有得到很好的研究，但促炎反应和病毒复制似乎受到控制，并且没有表现出明显的病理学。相比之下，人类感染会导致最初的高病毒载量，其特征是被称为细胞因子风暴的侵袭性促炎症反应。宿主和人类宿主感染过程中的主要区别是炎症反应。在这项研究中，我们应用一个简单的二元微分方程模型来研究促炎和抗炎反应，并应用详细的数学分析来识别参数空间中的特定区域，以获得单一稳定的地方性平衡、双稳态或周期解。将确定性模型扩展到两个随机模型，解释了在细胞（局部）或组织（全局）水平上看到的响应的可变性。随机模型的数值解表现出自然宿主中慢性感染或人类感染中细胞因子风暴的典型结果。在慢性感染中，当模型参数处于双稳态或周期解区域时，高响应和低响应之间偶尔会出现突然爆发。具有强烈的促炎反应和较弱的抗炎反应的细胞因子风暴发生在具有强促炎反应的单一稳定的地方性平衡的参数区域中。 模型分析和模拟的结果根据细胞因子的功能作用和自然宿主或人类宿主感染中观察到的炎症反应进行解释。