Milk-derived or recombinant transforming growth factor-beta has effects on immunological outcomes: a review of evidence from animal experimental studies

P>Identified factors from milk have been shown to improve health outcomes. One specific factor, transforming growth factor-Beta (TGF)-beta, has been identified previously as having the potential to impact on immunological outcomes in the newborn offspring. The primary objective of this review was to examine the published studies that have considered TGF-beta in association with immunological outcomes of experimental models. We hypothesized that oral administration of TGF-beta (through human milk, cow's milk, infant formula) or recombinant TGF-beta delivered via gavage, may down-regulate immune activation in newborn offspring. Animal experimental studies were identified through MEDLINE, CAB Abstracts, Biological Abstracts and Scopus. Selection criteria included well-described animal populations, sample and study design, source of TGF-beta, age and immunological outcomes measured and effect size. The findings were summarized temporally in tabular format, giving an overall measure of effect based on the literature available since 1994. Animal experimental studies (n=13) were included in the review to determine an association between maternal TGF-beta and immunological outcomes. Overall 92% of these studies (12/13) showed a positive association with TGF-beta 1 or TGF-beta 2, demonstrating protection against immunologically related outcomes in early life in an animal model. TGF-beta is important in developing and maintaining appropriate immune responses in the offspring. TGF-beta delivered orally to neonatal animals provides protection against adverse immunological outcomes, corroborating and supporting findings from human studies. Animal studies provide important clues to the pathogenesis and therapeutics of immune activation and allergy in early childhood. TGF-beta s are important growth factors involved in maintaining homeostasis in the intestine, regulating inflammation and allergy development and promoting oral tolerance in infants. Thus, taken as a whole, these and our other findings suggest that this cytokine in milk may influence the development of immunological outcomes in offspring.