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Mechanisms and Points of Control in the Spread of Inflammation: A Mathematical Investigation
Bulletin of Mathematical Biology ( IF 2.0 ) Pub Date : 2020-03-28 , DOI: 10.1007/s11538-020-00709-y
A Bayani 1 , J L Dunster 2 , J J Crofts 1 , M R Nelson 1
Affiliation  

Understanding the mechanisms that control the body’s response to inflammation is of key importance, due to its involvement in myriad medical conditions, including cancer, arthritis, Alzheimer’s disease and asthma. While resolving inflammation has historically been considered a passive process, since the turn of the century the hunt for novel therapeutic interventions has begun to focus upon active manipulation of constituent mechanisms, particularly involving the roles of apoptosing neutrophils, phagocytosing macrophages and anti-inflammatory mediators. Moreover, there is growing interest in how inflammatory damage can spread spatially due to the motility of inflammatory mediators and immune cells. For example, impaired neutrophil chemotaxis is implicated in causing chronic inflammation under trauma and in ageing, while neutrophil migration is an attractive therapeutic target in ailments such as chronic obstructive pulmonary disease. We extend an existing homogeneous model that captures interactions between inflammatory mediators, neutrophils and macrophages to incorporate spatial behaviour. Through bifurcation analysis and numerical simulation, we show that spatially inhomogeneous outcomes can present close to the switch from bistability to guaranteed resolution in the corresponding homogeneous model. Finally, we show how aberrant spatial mechanisms can play a role in the failure of inflammation to resolve and discuss our results within the broader context of seeking novel inflammatory treatments.

中文翻译:

炎症传播的机制和控制点:数学研究

了解控制身体对炎症反应的机制非常重要,因为炎症涉及多种疾病,包括癌症、关节炎、阿尔茨海默病和哮喘。虽然解决炎症在历史上一直被认为是一个被动的过程,但自世纪之交以来,寻找新的治疗干预措施已开始关注组成机制的主动操纵,特别是涉及凋亡中性粒细胞、吞噬巨噬细胞和抗炎介质的作用。此外,由于炎症介质和免疫细胞的运动性,人们对炎症损伤如何在空间上传播越来越感兴趣。例如,中性粒细胞趋化性受损与创伤和衰老引起的慢性炎症有关,而中性粒细胞迁移是慢性阻塞性肺疾病等疾病的一个有吸引力的治疗目标。我们扩展了现有的同质模型,该模型捕获炎症介质、中性粒细胞和巨噬细胞之间的相互作用,以纳入空间行为。通过分岔分析和数值模拟,我们表明空间不均匀的结果可以在相应的均匀模型中呈现接近从双稳态到保证分辨率的转换。最后,我们展示了异常空间机制如何在炎症失败中发挥作用,以在寻求新型炎症治疗的更广泛背景下解决和讨论我们的结果。我们扩展了现有的同质模型,该模型捕获炎症介质、中性粒细胞和巨噬细胞之间的相互作用,以纳入空间行为。通过分岔分析和数值模拟,我们表明空间不均匀的结果可以在相应的均匀模型中呈现接近从双稳态到保证分辨率的转换。最后,我们展示了异常空间机制如何在炎症失败中发挥作用,以在寻求新型炎症治疗的更广泛背景下解决和讨论我们的结果。我们扩展了现有的同质模型,该模型捕获炎症介质、中性粒细胞和巨噬细胞之间的相互作用,以纳入空间行为。通过分岔分析和数值模拟,我们表明空间不均匀的结果可以在相应的均匀模型中呈现接近从双稳态到保证分辨率的转换。最后,我们展示了异常空间机制如何在炎症失败中发挥作用,以在寻求新型炎症治疗的更广泛背景下解决和讨论我们的结果。我们表明,在相应的同质模型中,空间非同质结果可以接近从双稳态到保证分辨率的转换。最后,我们展示了异常空间机制如何在炎症失败中发挥作用,以在寻求新型炎症治疗的更广泛背景下解决和讨论我们的结果。我们表明,在相应的同质模型中,空间非同质结果可以接近从双稳态到保证分辨率的转换。最后,我们展示了异常空间机制如何在炎症失败中发挥作用,以在寻求新型炎症治疗的更广泛背景下解决和讨论我们的结果。
更新日期:2020-03-28
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