Evaluation of urinary tetranor-PGEM as biomarker of systemic inflammation

Abstract

Prostaglandin (PG) E2 is a lipid mediator with important functions during the onset of inflammation and the induction of inflammatory pain and fever. Levels of PGE2 reflect the severity of inflammatory disease and the effect of treatment. However, because of the fast metabolism of PGE2 and resulting methodological difficulties, it is not used as a diagnostic tool in clinical routine to date. We investigated whether the major urinary metabolite of PGE2, tetranor-PGEM, can be used as a clinical biomarker of inflammation and developed a simple and robust method using liquid chromatography coupled to mass spectrometry (LC-MS/MS) to directly assess and quantify this metabolite in patient material. In contrast to other approaches from the literature, our method does not require any derivatization steps prior to analyte extraction and determination. The sensitivity of our method is sufficiently high to determine baseline levels in spot urine samples of healthy volunteers. No significant changes of the tetranor-PGEM levels were detectable in these volunteers after a mild stimulus of inflammation by vaccination against the influenza A virus subtype H1N1. However, urinary tetranor-PGEM levels were more than tenfold increased in individuals suffering from systemic inflammation due to infection with respiratory syncytial virus (RSV). We conclude that tetranor-PGEM constitutes a robust biomarker of inflammation, which is highly up-regulated during systemic inflammatory reactions but not affected by nonpathogenic inflammatory stimuli. Routine assessment of urinary tetranor-PGEM may be used as a diagnostic tool to determine the severity of inflammatory reactions.