Leptin and EGF Supplementation Enhance the Immune System Maturation in Preterm Suckling Rats.

Paulina Torres-Castro,Margarida Castell,María J. Rodríguez-Lagunas,Lidia Marín-Morote,Francisco J. Pérez-Cano,Mar Abril-Gil,Àngels Franch,Blanca Grases-Pintó

doi:10.3390/nu11102380

Paulina Torres-Castro, Margarida Castell + Show 6 more

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https://doi.org/10.3390/nu11102380

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Abstract

In preterm newborns the immaturity of the immune system is remarkable, with reduced innate and adaptive immune responses. Many bioactive compounds in breast milk, such as growth factors and adipokines, contribute to the immune system’s maturation in early life. However, studies on the immunoregulatory activity in preterm neonates are practically nonexistent. The aim of the present study was to determine whether a nutritional supplementation in early life with leptin or epidermal growth factor (EGF) was able to promote the maturation of the systemic and intestinal immune system in preterm conditions. For this purpose, premature rats were daily supplemented by oral gavage with leptin or EGF. Term and Preterm groups receiving vehicle were used as controls. Preterm rats showed deficiencies compared to full-term ones, such as lower body weights, erythrocyte counts, plasma IgG and IgM concentrations and B cell percentages, and higher values of Th and Tc TCRαβ+ cells in mesenteric lymph nodes, and intestinal permeability, among others. However, leptin and EGF supplementation were able to revert some of these deficiencies and to improve the premature immune system’s development. These results suggest that leptin and EGF are involved in enhancing the maturation of the systemic and intestinal immune system in preterm conditions.

Highlights

Prematurity is one of the main causes of neonatal death
We have recently demonstrated in term rats that leptin and epidermal growth factor (EGF) supplementations during the suckling period are able to enhance early immune system development [21,22,23]
Relative weights of the spleen, thymus, and liver were not modified due to prematurity or supplementation, a decrease in relative small and large intestine length was observed in P+Leptin and

Summary

Introduction

Prematurity is one of the main causes of neonatal death. Advances in medicine over the years have enabled the survival of preterm newborns who would previously have died [1]. The third trimester is missed, triggering an incomplete development in the fetus and its organs, making these babies more susceptible to neural and respiratory problems, among other complications [2]. The gastrointestinal tract of term infants—which should develop in the last trimester—is immature at the time of birth, and more undeveloped in preterm newborns than in term ones. The underdeveloped intestine and other factors, such as the immature intestinal immune system, unestablished microbiota, or the high intestinal permeability, make the premature infant predisposed to suffering from necrotizing enterocolitis (NEC), a common disease in premature babies [3].

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