Cytokine Expression by Human Macrophage-Like Cells Derived from the Monocytic Cell Line THP-1 Differs between Treatment with Milk from Preterm- and Term-Delivering Mothers and Pasteurized Donor Milk

Veronique Demers-Mathieu,Robert K Huston,David C Dallas

doi:10.3390/molecules25102376

Veronique Demers-Mathieu, Robert K Huston + Show 1 more

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https://doi.org/10.3390/molecules25102376

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Journal: Molecules	Publication Date: May 20, 2020
Citations: 2	License type: CC BY 4.0

Affiliation: Randall Children's Hospital at Legacy Emanuel

Abstract

Immunomodulatory proteins from human milk may enhance the protection and development of the infant’s gut. This study compared the immunomodulatory effects of treatment with milk from preterm-(PM) and term-delivering (TM) mothers and pasteurized donor milk (DM) on cytokine gene expression in human macrophage-like cells derived from the monocytic cell line THP-1. The gene expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-12 (p40), IL-10 and GAPDH in macrophages treated with PM, TM and DM at steady and activated (inflammatory) states were measured using real-time reverse transcription-polymerase chain reaction. TNF-α and IL-6 in macrophages (both states) with DM were higher than PM or TM. IL-10 in steady state macrophages with DM was higher than PM whereas DM increased IL-10 in activated macrophages compared with TM. TM increased IL-6 and IL-12 (p40) in steady state macrophages compared with PM. IL-12 (p40) in activated macrophages with TM was higher than PM. IL-10 in steady state macrophages with TM was higher than PM. These results suggest that DM induces higher gene expression of pro-inflammatory and anti-inflammatory cytokines in macrophages compared with PM or TM. PM reduced gene expression of pro-inflammatory cytokines compared with TM, which may decrease the development of necrotizing enterocolitis and systematic inflammation.

Highlights

Mother’s milk contains numerous immune proteins and immune cells that enhance the protection and development of the infant immune system [1,2]
LPS) were lower in preterm infants compared with term infants [19]. These results suggest a potential association between the reduction of IL-6 production by mononuclear cells in preterm infants and their higher susceptibility of preterm infants to bacterial infection
The cell system cannot mimic the exposure of macrophages in the neonatal gastrointestinal tract during in vitro THP-1 cell system cannot mimic the exposure of macrophages in the neonatal gastrointestinal tract during breastfeeding, our findings provide preliminary information about differences in probreastfeeding, our findings provide preliminary information about differences in pro-inflammatory and anti-inflammatory cytokine expression in macrophage-like cells induced by preterm milk, term milk and pasteurized milk

Summary

Introduction

Mother’s milk contains numerous immune proteins (e.g., antibodies, lactoferrin and cytokines) and immune cells (e.g., macrophages, neutrophils, plasma cells, B cells and T cells) that enhance the protection and development of the infant immune system [1,2]. Preterm infants fed exclusively breast milk have lower risk of necrotizing enterocolitis (NEC) [3], infections [4] and sepsis [5] compared with those fed bovine-based milk products. This reduced risk is partially related to their exposure to the immune proteins from human milk. Another explanation of the elevated risk of infection in the first 2 months of postnatal age is that preterm infants receive lower levels of maternal transplacental pathogen-specific IgG than term infants [6]. Human milk immune components are critical for supporting the infant while its own innate and adaptive immune system is immature.

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