High levels of anti-inflammatory and pro-resolving lipid mediators lipoxins and resolvins and declining docosahexaenoic acid levels in human milk during the first month of lactation

Abstract

BackgroundThe fatty acid mixture of human milk is ideal for the newborn but little is known about its composition in the first few weeks of lactation. Of special interest are the levels of long-chain PUFAs (LCPUFAs), since these are essential for the newborn’s development. Additionally, the LCPUFAs arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are precursors for lipid mediators which regulate inflammation.MethodsWe determined the composition of 94 human milk samples from 30 mothers over the first month of lactation for fatty acids using GC-MS and quantified lipid mediators using HPLC-MS/MS.ResultsOver the four weeks period, DHA levels decreased, while levels of γC18:3 and αC18:3 steadily increased. Intriguingly, we found high concentrations of lipid mediators and their hydroxy fatty acid precursors in human milk, including pro-inflammatory leukotriene B4 (LTB4) and anti-inflammatory and pro-resolving lipoxin A4 (LXA4), resolvin D1 (RvD1) and resolvin E1 (RvE1). Lipid mediator levels were stable with the exception of two direct precursors.ConclusionsElevated levels of DHA right after birth might represent higher requirements of the newborn and the high content of anti-inflammatory and pro-resolving lipid mediators and their precursors may indicate their role in neonatal immunity and may be one of the reasons for the advantage of human milk over infant formula.

Effects of maternal n-3 fatty acid supplementation on placental cytokines, pro-resolving lipid mediators and their precursors

“…The amounts of SPMs detected in this study would equate to low-mid nanomolar tissue concentrations, which are biologically significant. SPMs and their precursors have also previously been detected in normal human plasma and lymphoid organs (Mas et al 2012, Markworth et al 2013, Colas et al 2014 and in human milk (Weiss et al 2013). Similar to our studies, markedly higher concentrations of the primary Rv precursors, 17-HDHA and 18-HEPE, were detected in these studies compared with their downstream products.…”

“…Circulating SPMs have been measured in healthy subjects (Mas et al 2012), with concentrations shown to be associated with n-3 PUFA intake (Colas et al 2014) and produced in greater amounts after exercise in patients taking ibuprofen (Markworth et al 2013). SPMs have been measured in breast milk (Weiss et al 2013), but to date have not been investigated in the context of human pregnancy.…”

Resolvin D1 Polarizes Primary Human Macrophages toward a Proresolution Phenotype through GPR32

“…PE-labeled anti-human CD80 Ab, allophycocyanin-labeled anti-human CD206 Ab, and the IgG1K isotype control were purchased from R&D Systems. RvD1 (7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid) produced by stereospecific total synthesis (23) was purchased from Cayman Chemicals (Ann Arbor, MI) and was verified by liquid chromatography-mass spectrometry/ mass spectrometry analysis in the laboratory (24).…”

ChemR23, the Receptor for Chemerin and Resolvin E1, Is Expressed and Functional on M1 but Not on M2 Macrophages

“…Chemerin Receptor 23, anti-human, mAb (ChemR23 Ab) and isotype IgG3, PE-labeled anti-human CD80, monoclonal allophycocyanin-labeled anti-human CD206 Ab, and the IgG1K isotype control were purchased from R&D Systems Europe. RvE1 (5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid) produced by stereospecific total synthesis (14) was purchased from Cayman Chemicals (Ann Arbor, MI) and was verified by liquid chromatography-tandem mass spectrometry analysis in the laboratory (29).…”