Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-36679-4
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Funding
- National Institutes of Health [P01GM095467, S10RR027926]
- USDA [2009-65200-05973]
- General Clinical Research Center, Penn State (NIH) [M01 RR 10732]
- Pronova BioPharma
- Penn State Clinical & Translational Research Institute, Pennsylvania State University CTSA, NIH/NCATS [UL1 TR000127]
- Baxter
- CSREES grant [2009-65200-05973]
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Specialized pro-resolving mediator(s) (SPMs) are produced from the endogenous omega-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and accelerate resolution of acute inflammation. We identified specific clusters of SPM in human plasma and serum using LC-MS/MS based lipid mediator (LM) metabololipidomics in two separate laboratories for inter-laboratory validation. The human plasma cluster consisted of resolvin (Rv)E1, RvD1, lipoxin (LX)B-4, 18-HEPE, and 17-HDHA, and the human serum cluster consisted of RvE1, RvD1, AT-LXA(4), 18-HEPE, and 17-HDHA. Human plasma and serum SPM clusters were increased after omega-3 supplementation (triglyceride dietary supplements or prescription ethyl esters) and low dose intravenous lipopolysaccharide (LPS) challenge. These results were corroborated by parallel determinations with the same coded samples in a second, separate laboratory using essentially identical metabololipidomic operational parameters. In these healthy subjects, two omega-3 supplementation protocols (Study A and Study B) temporally increased the SPM cluster throughout the endotoxin-challenge time course. Study A and Study B were randomized and Study B also had a crossover design with placebo and endotoxin challenge. Endotoxin challenge temporally regulated lipid mediator production in human serum, where pro-inflammatory eicosanoid (prostaglandins and thromboxane) concentrations peaked by 8 hours post-endotoxin and SPMs such as resolvins and lipoxins initially decreased by 2 h and were then elevated at 24 hours. In healthy adults given omega-3 supplementation, the plasma concentration of the SPM cluster (RvE1, RvD1, LXB4, 18-HEPE, and 17-HDHA) peaked at two hours post endotoxin challenge. These results from two separate laboratories with the same samples provide evidence for temporal production of specific pro-resolving mediators with omega-3 supplementation that together support the role of SPM in vivo in inflammation-resolution in humans.
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