Biosynthesis and analytics of specialized pro-resolving mediators: facts and faults

Specialized pro-resolving mediators (SPMs) have been suggested to act as key factors that mediate the resolution of inflammation. With the availability of synthetic standards, pharmacological studies have garnered support for the hypothesis. However, assessment of the catalytic properties of lipoxygenases as well as investigations of the signalling of the proposed SPM receptors raise serious doubt that SPMs are endogenous mediators of the resolution of inflammation. In line with this, careful evaluation of published data on SPM detection revealed a lack of evidence for many reported SPMs in biological samples due to analytical LC-MS/MS methods that do not meet the quality standards of the scientific community, or they rely on ELISAs that lack selectivity and are not suited for the establishment of the presence of SPMs in complex biological samples. Furthermore, artefacts due to autoxidation of PUFAs can be misinterpreted as SPM formation. In this review, we critically assess the published reports on the biosynthesis and the analysis of SPMs and summarize the current status in the field.