Resolving acute inflammation; what happens when inflammation goes haywire? How can it get back in line?

Abstract

Within this chapter we discuss the mechanisms that drive inflammation resolution and consider the possible reasons for the failure of resolution responses and chronicity of inflammation. We now know that the resolution of an acute inflammatory response is tightly controlled by a number of endogenously produced proresolving mediators that initiate tissue repair. These include resolvins, protectins, and maresins, collectively termed specialized proresolving lipid mediators (SPMs). These SPMs, which are derived from dietary lipids, stimulate endogenous inflammatory control mechanisms to accelerate resolution. This makes them important foci for dietary intervention and attractive targets for developing therapeutics for the prevention and treatment of inflammatory and infectious diseases. Herein we discuss some of the multifaceted actions of SPM including limiting neutrophil recruitment and switching the phenotype of macrophages to proresolution and repair. Importantly, SPMs also stimulate phagocyte function to contain and eliminate microbes and viruses to prevent the spread of infection and protect the host from tissue and organ damage. SPMs display potent and efficacious beneficial outcomes in preclinical animal models, indicating great therapeutic potential. SPMs enhance host defense and activate resolution circuits via specific G-protein-coupled receptors, which offer new targets for resolution pharmacology and drug development based on SPM agonists that drive resolution. We conclude by discussing how SPMs can be monitored as biomarkers and predictors of disease outcome and highlighting the promising results of SPM analogues that are currently in clinical trials.