Mechanisms and points of control in the spread of inflammation: a mathematical investigation

Bayani, A., Dunster, J. L. ORCID: https://orcid.org/0000-0001-8986-4902, Crofts, J. J. and Nelson, M. R. (2020) Mechanisms and points of control in the spread of inflammation: a mathematical investigation. Bulletin of Mathematical Biology, 82 (4). 45. ISSN 1522-9602 doi: 10.1007/s11538-020-00709-y

Abstract/Summary

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 in- volving the roles of apoptosing neutrophils, phagocytosing macrophages and anti-inflammatory mediators. Moreover, there is growing interest in how in-flammatory 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 abberant 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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/89845
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	Springer
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