Nguyen, Duc Ninh6; Sangild, Per Torp6; Østergaard, Mette Viberg7; Bering, Stine Brandt6; Chatterton, Dereck Edward Winston8
1 Dairy, Meat and Plant Product Technology, Department of Food Science, Faculty of Science, Københavns Universitet2 Clinical and Experimental Nutrition, Department of Nutrition, Exercise and Sports, Faculty of Science, Københavns Universitet3 Comparative Paediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, Københavns Universitet4 Clinical an Experimental Nutrition, Department of Human Nutrition, Faculty of Life Sciences, Københavns Universitet5 Ingredient and Dairy Technology, Department of Food Science, Faculty of Science, Københavns Universitet6 Comparative Paediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, Københavns Universitet7 Clinical an Experimental Nutrition, Department of Human Nutrition, Faculty of Life Sciences, Københavns Universitet8 Ingredient and Dairy Technology, Department of Food Science, Faculty of Science, Københavns Universitet
A balance between pro- and anti-inflammatory signals from the milk and microbiota controls intestinal homeostasis just after birth, and an optimal balance is particularly important for preterm neonates that are sensitive to necrotizing enterocolis (NEC). We suggest that the intestinal cytokine IL-8 plays an important role and hypothesize that transforming growth factor β2 (TGF-β2) acts in synergy with bacterial LPS to control IL-8 levels, thereby supporting intestinal homeostasis. Preterm pigs were fed colostrum (containing TGF-β2) or infant formula with or without antibiotics (COLOS, n = 27; ANTI, n = 11; IF, n = 40). Intestinal IL-8 levels and NEC incidence were much higher in IF than in COLOS and ANTI pigs (P < 0.001), but IL-8 levels did not correlate with NEC severity. Intestinal TGF-β2 levels were high in COLOS, but low in IF and ANTI pigs. Based on these observations, the interplay among IL-8, TGF-β2 and LPS was investigated in a porcine intestinal epithelial cell line. TGF-β2 attenuated LPS-induced IL-6, IL-1β and TNF-α release by reducing early ERK activation, whereas IL-8 secretion was synergistically induced by LPS and TGF-β2 via NF-κB. The TGF-β2/LPS-induced IL-8 levels stimulated cell proliferation and migration following epithelial injury, without continuous NF-κB activation and COX-2 expression. We suggest that a combined TGF-β2/LPS induction of IL-8 stimulates epithelial repair just after birth when the intestine is first exposed to colonizing bacteria and TGF-β2-containing milk. Moderate IL-8 levels may act to control intestinal inflammation, while excessive IL-8 production may enhance the damaging pro-inflammatory cascade leading to NEC.
American Journal of Physiology: Gastrointestinal and Liver Physiology, 2014, Vol 307, Issue 7