Dynamics of the HPA axis and inflammatory cytokines: Insights from mathematical modeling
Dynamics of the HPA axis and inflammatory cytokines: Insights from mathematical modeling
复制标题
DOI：
10.1016/j.compbiomed.2015.09.018
复制
发表时间：
2015-12-01
影响因子：
7.7
通讯作者：
Zaringhalam, Jalal
中科院分区：
文献类型：
--
作者：
Malek, Hamed;Ebadzadeh, Mohammad Mehdi;Zaringhalam, Jalal
在这里提出的工作中，开发了一种新的数学模型来探索急性炎症中下丘脑-垂体-肾上腺（HPA）轴和炎性细胞因子之间的双向通信。动态模型由两种主要促炎细胞因子（TNF-α和IL-6）和HPA轴的两种激素（ACTH和皮质醇）和LPS内毒素的五个延迟微分方程5D组成。该模型是一种尝试，以增加对初级激素和细胞因子在这种复杂的关系中的作用的理解，通过展示不同的器官和激素在炎症反应的调节中的影响。该模型捕获的主要定性特征的细胞因子和激素动力学时，引入了毒性的挑战。此外，在这项工作中，一个新的简单的延迟模型的HPA轴的介绍，这支持的理解，在正常和感染条件下的HPA激素的超昼夜节律。通过使用该模型进行模拟，通过稳定性分析研究了关键炎性细胞因子和皮质醇在从急性炎症向持续性炎症转变中的作用。此外，通过采用马尔可夫链蒙特卡罗（MCMC）方法，参数的不确定性和参数的变化对彼此的影响进行了分析。该模型证实了HPA轴在急性和长期炎症中的重要作用，并且可以成为进一步研究应激对感染性疾病免疫反应的作用的有用工具。(C)2015爱思唯尔有限公司版权所有。
In the work presented here, a novel mathematical model was developed to explore the bi-directional communication between the hypothalamic-pituitary-adrenal (HPA) axis and inflammatory cytokines in acute inflammation. The dynamic model consists of five delay differential equations 5D for two main proinflammatory cytokines (TNF-alpha and IL-6) and two hormones of the HPA.axis (ACTH and cortisol) and LPS endotoxin. The model is an attempt to increase the understanding of the role of primary hormones and cytokines in this complex relationship by demonstrating the influence of different organs and hormones in the regulation of the inflammatory response. The model captures the main qualitative features of cytokine and hormone dynamics when a toxic challenge is introduced. Moreover, in this work a new simple delayed model of the HPA axis is introduced which supports the understanding of the ultradian rhythm of HPA hormones both in normal and infection conditions. Through simulations using the model, the role of key inflammatory cytokines and cortisol in transition from acute to persistent inflammation through stability analysis is investigated. Also, by employing a Markov chain Monte Carlo (MCMC) method, parameter uncertainty and the effects of parameter variations on each other are analyzed. This model confirms the important role of the HPA axis in acute and prolonged inflammation and can be a useful tool in further investigation of the role of stress on the immune response to infectious diseases. (C) 2015 Elsevier Ltd. All rights reserved.