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

ObjectiveThe 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.MethodsParticipants 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 75thpercentile. Multivariate logistic regression models were used to examine associations between maternal-infant characteristics, inflammatory markers, and IMEP.ResultsThresholds of elevated Na and Na/K ratios at the 75thpercentile 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 > 75thpercentile 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 >75thpercentile. IMEP also moderated associations between maternal-infant characteristics and inflammatory markers.DiscussionThis study demonstrates the importance of mammary epithelium permeability measurement for the interpretation of human milk inflammatory profiles during established lactation.