Temporal Trends in the Inflammatory Cytokine Profile of Human Breastmilk

Abstract

A longer lifetime duration of breastfeeding may decrease the risk of breast cancer by reducing breast inflammation and mitigating inflammatory cytokine expression during postlactational involution. However, little is known about how the inflammatory cytokine profile in human breastmilk changes over time. To study temporal trends in breastmilk cytokine expression, we measured 80 human cytokines in the whey fraction of breastmilk samples from 15 mothers at 1, 4, 8, and 12 weeks postpartum. We used mixed models to identify temporal changes in cytokine expression and investigated parity status (multiparous vs. primiparous) as a potential confounder. Nine cytokines (monocyte chemoattractant protein-1, epithelial-derived neutrophil-activating protein-78, hepatocyte growth factor, insulin-like growth factor-binding protein-1, interleukin-16, interleukin-8, macrophage colony-stimulating factor, osteoprotegerin, and tissue inhibitor of metallopeptidase-2) had significantly decreased expression with increasing breastfeeding duration; all nine have known roles in breast involution, inflammation, and cancer and may serve as biomarkers of changing breast microenvironment. No cytokine significantly increased in level over the study period. Total protein concentration significantly decreased over time (p<0.0001), which may mediate the association between length of breastfeeding and inflammatory cytokine expression. Parity status did not confound temporal trends, but levels of several cytokines were significantly higher among multiparous versus primiparous women. Our results suggest that inflammatory cytokine expression during lactation is dynamic, and expressed milk may provide a noninvasive window into the extensive biological changes that occur in the postpartum breast.

Maternal and pregnancy-related factors affecting human milk cytokines among Peruvian mothers bearing low-birth-weight neonates

“…Consistent with other studies, we found that many cytokines are present in detectable levels in human milk and in higher concentrations in colostrum (Agarwal et al, 2011; Castellote et al, 2011; Chollet-Hinton et al, 2014; Hawkes et al, 2000; Trend et al, 2016). Chemokines associated with innate immunity (MCP-1, MIP-1β, IP-10, IL-8, RANTES) and cytokines that impact epithelial cell function (TGF-βs) or induce lymphocyte maturation (IL-6 and IL-7) were almost universally detectable.…”

Subclinical mastitis occurs frequently in association with dramatic changes in inflammatory/anti-inflammatory breast milk components

“…Whereas cytokine expression decreases during the first month of lactation in transitional breast milk, immune components appear relatively stable in mature breast milk [21].…”

Oropharyngeal Colostrum Administration in Very Low Birth Weight Infants: A Randomized Controlled Trial*

“…Colostrum is the first milk produced by the mammary when the tight junctions in the mammary epithelium are open (1). It is rich in cytokines (anti-inflammatory cytokines, pro-inflammatory cytokines) and other immune agents such as secretory Immunoglobulin A (sIgA) and lactoferrin (2)(3)(4)(5)(6)(7). These immune agents can provide bacteriostatic, bactericidal, antiviral, anti-inflammatory and immunomodulatory protection against infection (8).…”