What Mediates the Inflammation Resolution?

Abstract

The concept of specialized proresolving lipid mediators (SPMs) is such a perfect model: Different enzymes of the arachidonic acid cascade lead to formation of specific multiply hydroxylated PUFAs. These SPM stop inflammation at high potency through the binding to G-protein-coupled receptors (GPCRs). 1 A year ago we showed, based on own data and current lit-erature, that neither the formation routes of trihydroxylated specialized proresolving lipid mediators such as lipoxins and resolvins via lipoxygenases are convincing nor the signaling through particular GPCRs has been conclusively demonstrated. 2 This challenges the biological role of these SPMs. However, most attention focused on the finding that analytical methods to demonstrate their formation and occurrence in biological samples are inappropriate, while methods validated accord-ing to internationally agreed standards largely fail to detect the molecules. 2 − 4 Although this started an intense discussion, our questions regarding the formation route, the signaling, and the validity of detection methods have not yet been addressed. Meanwhile, many SPM papers, which show “illustrations” of LC–MS chro-matograms instead of original data are marked in PubPeer but theauthorsareyettoprovideoriginaldatatoprovetheexistence of SPMs in their samples. Instead, arguments such as the testing of SPM in clinical trials, the own h -index or the number of SPM