Cytokines in milk and the role of TGF-beta

Abstract

Cytokines are required for normal growth and development of the mammary gland and TGF-β prominently represents an established effector of apoptosis, e.g., during involution of the mammary gland. By the control of intracellular signaling pathways, including JAK/STAT, MAPK, PI-3K, and NF-κB, cytokines efficiently regulate cell proliferation and inflammation in the breast. Therefore, cytokines are discussed also in a context of malignant mammary growth. As a group of tissue hormones produced by somatic cells or by cells from the immune system, cytokines are defined by their immunomodulatory potential. Over the past 40 years, multiple cytokines were identified in colostrum and milk. Importantly, cytokines derived from mammary secretions after birth are required for maturation of the immune system in the developing gastrointestinal tract from the suckling. Moreover, recent studies have further assessed the particular interactions between probiotic bacterial strains and cytokines. In light of the increasing prevalence of inflammatory diseases of the gastrointestinal system, the effects of probiotic microorganisms during milk fermentation may have immunotherapeutic potential in the future.

More than sugar in the milk: human milk oligosaccharides as essential bioactive molecules in breast milk and current insight in beneficial effects

“…Cytokines and chemokines found in breast milk can pass the intestinal barrier, protect and contribute to immune development in the systemic circulation of the infant (Dawod and Marshall 2019). Cytokines in human milk have been shown to expedite immune maturation, to defend against infections, and to prevent inflammation (Brenmoehl et al 2018). The most abundant cytokine in breast milk is Transforming Growth Factor-b (TGF-b) (Sitarik et al 2017).…”

“…The most abundant cytokine in breast milk is Transforming Growth Factor-b (TGF-b) (Sitarik et al 2017). TGF-b attenuates too strong immune responses and induces tolerogenic signals, which may be instrumental in preventing allergic diseases (Brenmoehl et al 2018). However, the key anti-inflammatory and immunoregulatory cytokine interleukin-10 (IL-10), is found in very high concentrations during the first 80 hours of lactation (Garofalo et al 1995).…”

“…TNF-a, IL-6, IL-8, and interferon-c (IFN-c) have all been found in human milk, and they generally decrease in concentration over the course of lactation (Meki et al 2003). The function of the proinflammatory cytokines in human milk is still a subject of debate, but it probably contributes to intestinal development and maturation of immune cells in the infants gastrointestinal tract (Brenmoehl et al 2018).…”

The Impact of Parturition Induction With Cloprostenol on Immunological Parameters in the Sow Colostrum

“…The cytokine analysis in this study revealed higher concentrations of IL-1β and TNFα in colostrum from sows with parturition induced by cloprostenol, compared to colostrum from sows with non-induced parturition. In human colostrum, IL-1β stimulates the secretion of TNFα by monocytes and helper T cells, leading to the production of pro-in ammatory cytokines stimulating macrophages and consequently establishing cellular immunity in newborns [31]. TNFα by itself stimulates mucin secretion in gut epithelia [32].…”

Does Caesarean Section or Preterm Delivery Influence TGF-β2 Concentrations in Human Colostrum?

“…TGF-β also regulates lymphocytes' T responses, leading to better gut tolerance [7]. Furthermore, TGF-β2 can inhibit the inflammatory response in immature human intestinal epithelial cells and suppress the expression of macrophage cytokines, thereby reducing the risk of necrotizing enterocolitis (NEC) in preterm neonates [15][16][17]. On the other hand, there are also data suggesting that higher levels of TGF-β2 may be related to NEC [18].…”