Resolution of chronic inflammatory disease: universal and tissue-specific concepts

Abstract

Inflammation and its resolution is under-studied in medicine despite being essential for understanding the development of chronic inflammatory disease. In this review article, we discuss the resolution of inflammation in both a biological and translational context. We introduce the concept of impaired resolution leading to diseases like rheumatoid arthritis, Crohn's disease, and asthma, as well as the cellular and molecular components that contribute to resolution of joint, gut, and lung inflammation, respectively. Finally, we discuss potential intervention strategies for fostering the resolution process, and their implications for the therapy of inflammatory diseases.

Fig. 1

Activation, resolution, and the process leading to chronicity of inflammation. Time course of the inflammatory response with activation phase, peak phase, and resolution phase. Failure of resolution leads to chronic inflammatory diseases. Key cells of the activation and resolution phase are shown in the gray squares. ILC innate lymphoid cells, TH17 T helper cells 17, MΦ macrophages

Fig. 2

Functional resolution map. Map of resolution with key mechanisms (bright gray squares), cells (blue squares), and molecules (dark gray squares). AAM alternatively activated macrophage, AMPK adenosine monophosphate-activated protein kinase, ILC innate lymphoid cells, IL interleukin, LPX lipoxin, MΦ macrophages, PMN polymorphonuclear neutrophils, TGF transforming growth factor, TRAIL tumor necrosis factor-related apoptosis inducing ligand, FASL Fas ligand, ROS reactive oxygen species