Pro-inflammatory cytokines and growth factors in human milk: Associations with increased mammary epithelium permeability during established lactation

Abstract

Objective: The inflammatory signature of human milk is an indicator of mammary gland health and has implications for infant nutrition, growth, and immune system development. We hypothesized that measurement of mammary epithelium permeability would provide important context for the interpretation of the inflammatory signature of human milk. Methods: Participants were drawn from a previous study of human milk cytokines and growth factors. Analysis included 162 participants (98 Black women, 64 White women) with infants ranging from 1-18 months of age. Levels of twelve inflammatory markers (IL-6, IL8, TNFα, IL-1β, FASL, VEGFD, FLT1, BFGF, PLGF, EGF, leptin, adiponectin) were evaluated previously. Milk sodium (Na) and potassium (K) were measured with ion selective probes. Increased mammary epithelium permeability (IMEP) was indicated by either Na levels or Na/K ratios greater than the 75th percentile. Multivariate logistic regression models were used to examine associations between maternal-infant characteristics, inflammatory markers, and IMEP. Results: Thresholds of elevated Na and Na/K ratios at the 75th percentile were found to be 8.0 mmol/L and 0.53 respectively. IMEP was most frequent (42.6%) during early lactation (1-3 months). The strongest predictors of IMEP as defined by Na > 75th percentile were infant age, Black race, IL6, and BFGF, while maternal age and PLGF were important predictors of IMEP as defined by the Na/K ratio >75th percentile. IMEP also moderated associations between maternal-infant characteristics and inflammatory markers. Discussion: This study demonstrates the importance of mammary epithelium permeability measurement for the interpretation of human milk inflammatory profiles during established lactation.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was funded by the College of Natural Sciences, University of Massachusetts-Amherst.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The institutional review board (IRB) of the University of Massachusetts Amherst gave ethical approval for this work.

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Data Availability

All data produced in the present study are available upon reasonable request to the authors.

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