Polyunsaturated Fatty Acid-Derived Lipid Mediators as Biomarkers in Critical Care

Abstract

Inflammation is a necessary and beneficial process that protects against injury and infection. However, dysregulated and unrestrained inflammation underpins nearly every pathology related to critical illness. Inflammation is increasingly understood as a coordinated phenomenon between pro-inflammatory processes and restorative resolution of inflammation, both working in concert to restore homeostasis. There is a growing body of literature supporting the concept that resolution is controlled by derivatives of dietary polyunsaturated fatty acids termed specialized pro-resolving lipid mediators (SPMs) and that pathologic inflammatory processes are characterized by absence or dysregulation of SPMs leading to failure of inflammatory resolution. In this chapter, we will discuss the role of SPMs in several diseases frequently encountered in the ICU – including sepsis, ARDS, and viral illness, specifically influenza – and their potential uses as diagnostic and prognostic biomarkers. This discussion will provide a framework to discuss how emerging research implicates SPMs and polyunsaturated fatty acids in the clinical manifestations of COVID-19, itself a viral illness that causes sepsis and ARDS. Therapies modulating SPMs and SPMs themselves are emerging as candidate therapeutic molecules that may dampen pro-inflammatory cytokine storms, promote resolution of inflammation, and induce a return to homeostasis in COVID-19 and other severe illnesses caused by aberrant inflammation.KeywordsSpecialized pro-resolving mediatorSepsisAcute respiratory distress syndromeCOVID-19n-3 polyunsaturated fatty acidsn-6 polyunsaturated fatty acidsArachidonic acidDocosahexaenoic acidEicosapentaenoic acidResolvinsMaresinsProtectinsLipoxins