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.
Highlights
Acute inflammation is essential to health, being the body’s response to damage, infection and foreign material; when dysregulated, inflammation can fail to resolve and, as such, contributes to a large variety of pathophysiological processes
Diseases characterised by chronic inflammation may be linked to the inability of acute inflammation to resolve, and specific pro-resolution pathways are seen as alternative therapeutic targets (Fullerton and Gilroy 2016; Sugimoto et al 2016); in addition, there is growing experimental evidence that the inflammatory response is characterised by spatial changes and that mechanisms such as cell motility are key in identifying how inflammatory conditions progress (Luster et al 2005; Eming et al 2007; Nourshargh et al 2016; Jasper et al 2019)
In this work we have extended an existing homogeneous model of the acute inflammatory response to include the spatial effects of cell motility and mediator diffusion
Summary
Acute inflammation is essential to health, being the body’s response to damage, infection and foreign material; when dysregulated, inflammation can fail to resolve and, as such, contributes to a large variety of pathophysiological processes. The balance between the cellular components of inflammation is orchestrated via a variety of pro- and anti-inflammatory mediators that, combined with the interactions between neutrophils and macrophages, control the progression of inflammation to healthy resolution or a chronic, self-perpetuating condition. Diseases characterised by chronic inflammation may be linked to the inability of acute inflammation to resolve, and specific pro-resolution pathways are seen as alternative therapeutic targets (Fullerton and Gilroy 2016; Sugimoto et al 2016); in addition, there is growing experimental evidence that the inflammatory response is characterised by spatial changes and that mechanisms such as cell motility are key in identifying how inflammatory conditions progress (Luster et al 2005; Eming et al 2007; Nourshargh et al 2016; Jasper et al 2019). There is a growing need to elucidate the mechanisms that control the interactions between the distinct cell types that drive the resolution of inflammation and, in particular, how spatial effects such as cell motility effect inflammatory outcomes, since the potential to actively manipulate these aspects of the inflammatory response exhibits great scope for development of new drugs and treatments (Libby 2007; Hunter 2012)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
