Cytokines and growth factors in the developing intestine and during necrotizing enterocolitis

Abstract

Cytokines and growth factors play diverse roles in the uninflamed fetal/neonatal intestinal mucosa and in the development of inflammatory bowel injury during necrotizing enterocolitis (NEC). During gestational development and the early neonatal period, the fetal/premature intestine is exposed to high levels of many "inflammatory" cytokines and growth factors, first via swallowed amniotic fluid in utero and then, after birth, in colostrum and mother's milk. This article reviews the dual, seemingly counter-intuitive roles of cytokines, where these agents play a "trophic" role and promote maturation of the uninflamed mucosa, but can also cause inflammation and promote intestinal injury during NEC.

Keywords: Cytokines; Growth factors; Intestinal injury; NEC; Prevention.

Fig. 1

Human fetal intestine expresses several inflammatory cytokines and transcriptional regulators at higher levels than in the adult intestine. Bar diagram (means + standard errors) show fold change in mRNA expression (normalized against the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase). Broken line represents mRNA levels in the adult intestine. De-identified human fetal intestine was obtained at medical terminations (n = 8/group) and the adult intestine from subjects undergoing bariatric surgery (n = 5). The study was deemed to be “no human subjects” research by the Institutional Review Board. Crossing-threshold cycle numbers in the 2 groups were compared by Mann–Whitney U test. *P < 0.05.

Fig. 2

Cytokine expression in surgically-resected bowel specimens of NEC and uninflamed human neonatal intestine. Deidentified microarray data from NEC (n = 4) and uninflamed neonatal intestine (tissue resected for intestinal obstruction or during ostomy repair; n = 4) were downloaded from the public database Gene Expression Omnibus and analyzed using the software program Partek Genomics Suite 6.6 (Partek, St. Louis, MO). Boxplots show means ± standard errors of the expression intensity of the cytokine probe sets. Tissue samples of NEC are depicted in red squares, whereas the uninflamed neonatal intestine is shown as green triangles. Groups were compared by analysis of variance. *P < 0.05. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)