Macrophage Polarization Determines Inflammation Amplification and Resolution

Sterile inflammation is a form of pathogen-free inflammation caused by non-infectious stimuli, such as injury, toxins, or cell stress. It serves to protect tissues, promote repair, and restore homeostasis. Like other forms of inflammation, sterile inflammation has three distinct stages: initiation, amplification, and resolution. The transition between the last two phases is particularly important for restoring tissue balance. If this process is disrupted, it can lead to the development of chronic inflammation and various diseases. Although the exact mechanisms that control this transition in the process of sterile inflammation are not fully understood, they remain a key area of research. In this work, we develop a mathematical model to explore the interplay between pro- and anti-inflammatory mediators in the process of sterile inflammation. The model consists of an integro-differential reaction-diffusion system that captures the spatial and temporal evolution of inflammation within tissue and blood. Specifically, the model tracks the concentrations of seventeen key-players involved in the inflammatory response, including circulating macrophages, DAMPs, RAMPs, inflammatory cytokines, and tissue-resident macrophages (TRMs). We focus on the role of macrophage polarization in determining the outcome of sterile inflammation, whether it leads to resolution or chronicity. According to this model, the anti-inflammatory processes, namely the inhibition in polarization of M1-type macrophages, can lead to the resolution of inflammation.