Quantitative Time-Dependent Variability and Independent Correlation of Eicosanoids in Human Plasma

Abstract

Purpose: Eicosanoids are small molecule lipid mediators of inflammation that, until recently, could not be measured in a high-throughput fashion or with high-resolution coverage. Eicosanoid-centric inflammation and related pathways have been implicated in the development of both acute and chronic major morbid conditions. Thus, eicosanoids hold promise as valuable biomarkers of disease risk. However, eicosanoid variability within and between individuals is not well understood. This knowledge gap limits the interpretability of detectable eicosanoid levels. Methods: We performed peripheral blood eicosanoid sampling repeatedly in a cohort of 27 healthy individuals over the course of a year. Using these data, we conducted a comprehensive longitudinal analysis of the inter- and intra-individual variability of eicosanoids over time. Results: We found that 79.2% of peripherally circulating eicosanoids were relatively stable over time. The vast majority of the over 700 eicosanoids that were repeatedly measurable demonstrated variability coefficients of < 0.5 (standard deviation / mean). There was less variation within individuals than between individuals. Cluster analyses revealed distinct groups of intercorrelated eicosanoids that demonstrated stable connectivity across individuals. Among these stable groups of eicosanoids, certain sentinel eicosanoids were identified as independently highly correlated with other eicosanoids with a group in a manner that was also consistently found across individuals. Conclusions: Our results indicate that detectable and quantifiable eicosanoids in the human peripheral circulation are largely stable over time. Importantly, patterns of eicosanoid stability include persistent intercorrelated clusters that include sentinel eicosanoid species that demonstrate a consistently high independent correlation with many other eicosanoids. These sentinel eicosanoids may represent particularly important candidate markers or targets for further investigation of inflammation-related human disease.