Maternal milk regulation of cell infiltration and interleukin 18 in the intestine of suckling rat pups

• Published in: Gut Vol. 52; no. 11; pp. 1579 - 1586
• Main Authors: Penttila, I A, Flesch, I E A, McCue, A L, Powell, B C, Zhou, F H, Read, L C, Zola, H
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01-11-2003; BMJ; BMJ Publishing Group Ltd; BMJ Publishing Group LTD; Copyright 2003 by Gut
• Subjects: Analysis; Animals; Animals, Suckling; Antigens; Antigens, CD - immunology; Biological and medical sciences; Blotting, Western - methods; bovine serum albumin; Breast milk; BSA; Cell Count - methods; Crohns disease; Cy3; Cytokines; Dendritic cells; Dendritic Cells - immunology; Down-Regulation - immunology; Eosinophils - immunology; Experiments; Female; Fluorescent Antibody Technique - methods; Food; Fundamental and applied biological sciences. Psychology; Fundamental immunology; GAPDH; glyceraldehyde-3-phosphate dehydrogenase; Hospitals; IFN-γ; IL-18; IL-1ra; Ileum - immunology; immune development; Immune response; Immune system; Immunobiology; Immunological tolerance; indocarbocyanine; Inflammation; Influence; interferon γ; interleukin 1 receptor antagonist; Interleukin-18; Interleukin-18 - analysis; Interleukin-18 - immunology; Intestinal Immunology; Intestinal Mucosa - immunology; Intestine, Small - immunology; Lymphocyte Activation - immunology; Lymphocytes; Mast Cells - immunology; milk; Milk - immunology; Neonatology; Nutritional aspects; PBS; phosphate buffered saline; Physiological aspects; Physiology; Polyethylene; rat mast cell protease II; Rats; Rats, Wistar; RMCP II; RNA, Messenger - analysis; Rodents; Small intestine; T helper cell type 1; T helper cell type 2; TGF-β; Th1; Th2; Transforming Growth Factor beta - analysis; Transforming Growth Factor beta - immunology; transforming growth factor β; Tropical medicine; Up-Regulation - immunology; Australia; Oceania; Melbourne Victoria Australia; Human; Rat; Digestive system; Transforming growth factor β; Mucosa; Rodentia; Gut; Infant; Biosynthesis; Experimental study; Biological activity; Interleukin 18; Vertebrata; Regulation(control); Immunology; Mammalia; Animal; Content; Immune tolerance; Breast milk
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.52.11.1579

Background and aims: In neonates the gastrointestinal tract is exposed to food and bacterial antigens at a time when the gut mucosal immune system has not developed the ability to induce oral tolerance. This increases the risk for an inappropriate immune response to oral antigens. Transforming growth factor β (TGF-β) is an immunoregulatory cytokine present in high concentration in maternal milk. Interleukin 18 (IL-18) is a cytokine that mediates early immune events, and drives T cell development. We assessed the role of TGF-β in mediating mucosal immune development and specifically the effect on endogenous IL-18. Methods: Rat pups were randomly assigned to the following groups, naturally suckled, maternal milk via cannula, and formula fed with and without physiological levels of TGF-β2. A comparison of the immune response profile was then carried out. Cytokine profiles, dendritic cell, intestinal mast cell, and eosinophil numbers were assessed. Results: We show that feeding formula deficient in TGF-β2 resulted in accumulated IL-18 protein release from intestinal epithelial cells and IL-18 mRNA up regulation. A proinflammatory cytokine profile resulted in the gut, along with increased numbers of activated dendritic cells, eosinophils, and mast cells. Supplementation of the formula with TGF-β2 down regulated the proinflammatory cytokine mRNA as well as the number of activated lymphocytes, eosinophils, mast cells, CD80, and CD86 positive dendritic cells. Conclusion: The data suggests an important role for maternal milk, in regulating immune responses after exposure to food antigens, which might otherwise induce deleterious immune responses in the intestine of suckling neonates. This regulation is potentially mediated by milk TGF-β2, as well as endogenous IL-18.