Mechanisms and Points of Control in the Spread of Inflammation: A Mathematical Investigation
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Mechanisms and Points of Control in the Spread of Inflammation: A Mathematical Investigation A. Bayani1 · J. L. Dunster2 · J. J. Crofts1 · M. R. Nelson1 Received: 28 November 2019 / Accepted: 14 February 2020 © The Author(s) 2020
Abstract 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. Keywords Inflammation · Resolution · Mathematical modelling · Chemotaxis · Partial differential equations
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M. R. Nelson [email protected]
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Department of Physics and Mathematics, Nottingham Trent University, Clifton Campus, Nottingham NG11 8NS, UK
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Institute for Cardiovascular and Metabolic Research, University of Reading, Reading RG6 6AS, UK 0123456789().: V,-vol
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1 Introduction Acute inflammation is essential to health, being the body’s response to damage, infection and foreign material; however, when dysregulated, inflammation can fail to resolve and, as such, contributes to a large variety of pathophysiological processes. While the range of pathologies that feature or arise from inflammation vary greatly (from cancer, to diabetes, to arthritis to name just a few), the cellular and chemical pathways that characterise the inflammatory response remain similar across conditions (Libby 2007). The initial inflammatory response primarily starts in the vasculature where leucocytes [neutrophils and monocytes (precursors of macrophages)] migrate into damaged tissue. Neutrophils are recruited into tissue early; these are short-lived cells that release substances that can kill bacteria but which can also be harmful to otherwise healthy ti
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