Mead Johnson Symposium: Functional Proteins in Human Milk: Role in Infant Health and Development

Abstract

From the Department of Nutrition, Harvard Medical School, Harvard School of Public n this inaugural conference on the emerging roles of functional proteins in pediatric nutrition, established experts were asked to review basic and clinical research studies on functional proteins such as lactoferrin, lactalbumin, growth factors such as epidermal growth factor, and on transforming growth factor-beta (TGF-b) and other cytokines found in breast milk. In addition, a newly reported functional protein in breast milk, adiponectin, was considered. Initially, in an overview presentation, Dr. Allan Walker from Boston considered the ‘‘gold standard’’ for functional protein nutrition by reviewing the role of breast milk components in the passive protection and active stimulation of intestinal defenses in the nursing human neonate. This was followed by a comprehensive review by Professor Per Brandtzaeg on human milk and its specific role in activating the mucosal immune system, including the stimulation of an important protective immunogolubulin, sIgA, on mucosal surfaces, as well as the collective activation of a balanced T helper cell response, including the stimulation of T regulatory cells. These overviews lay the ground work for subsequent discussion of specific functional proteins in pediatric nutrition. In a session devoted to TGF-b in human milk, 4 speakers reviewed the extensive influence that this regulatory cytokine, present in varying amounts in human milk, has on the mucosal immune system and host defense. Dr. John Letterio from Case Western Reserve Medical School reviewed the extensive literature on TGF-b1, the principal regulatory cytokine produced by lymphoid cells. He suggested that under different microenvironmental conditions or with different types of lymphoid cells, TGF-b1 can have either inhibitory or stimulatory effects. He suggested that polymorphisms of signaling molecules of TGF-b, SMAD 6 or 7, can contribute to the expression of clinical conditions such as inflammatory bowel disease. Next, Dr. Samuli Rautava from the University of Turku in Finland reviewed his recent work with TGF-b2, the predominate form of TGF-b in breast milk, on inflammation in human models for the developing intestine. He reported that preincubation or concurrent incubation of TGF-b2 at levels found in human milk, could inhibit the intestinal inflammatory response to IL-1b as measured by IL-8 production in human fetal small intestinal xenografts after exposure to the inflammatory cytokine IL-1b. He further suggested that the inhibitory response was mediated by SMAD6 and involved the ERK signaling pathway. Dr. Imme Penttila from Adelaide, Australia, re-