Human β-defensin 2 expression in ELBW infants with severe necrotizing enterocolitis.
BACKGROUND
The aim of this study was to analyze whether the mucosal innate immune response of extremely-low-birth-weight (ELBW) infants might play a role in the development of necrotizing enterocolitis (NEC).


METHODS
Between April 2008 and December 2009 antimicrobial peptides were prospectively measured in fecal samples of ELBW infants. In cases requiring abdominal surgery, full-thickness gut biopsies were analyzed for expression of human β-defensin 2 (hBD2), interleukin-8 (IL-8), villin, MD2, and Toll-like receptor 4 (TLR4).


RESULTS
Fecal hBD1 concentrations were consistently low in all patients, whereas hBD2 concentrations were high in meconium, particularly in clinical chorioamnionitis, and then dropped, followed by a steady increase after day 14. Infants with moderate NEC showed significantly increased fecal hBD2 concentrations before clinical symptoms, in contrast to infants developing severe NEC. Analysis of intestinal resection material obtained from patients with severe NEC revealed low hBD2 mRNA and protein levels, and increased expression of the inflammatory cytokine IL-8.


CONCLUSIONS
High hBD2 concentrations, reflecting strong intestinal immune responses, were associated with moderate courses of the disease. In severe NEC, low hBD2 expression was accompanied by low TLR4/MD2 expression, suggesting an inadequate response to luminal bacteria, possibly predisposing those infants to the development of NEC.
Department of Neonatology, HELIOS Children's Hospital, Witten/Herdecke University, Wuppertal, Germany. andreas.jenke@helios-kliniken.de
Andreas C W
AC
Jenke
Matthias
M
Zilbauer
Jan
J
Postberg
Stefan
S
Wirth
D000704:Analysis of Variance; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D020345:Enterocolitis, Necrotizing / Q000453:epidemiology / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000601:surgery; D005243:Feces / Q000737:chemistry; D005260:Female; D005786:Gene Expression Regulation; D005858:Germany / Q000453:epidemiology; D005865:Gestational Age; D006801:Humans; D018928:Immunity, Mucosal; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism*; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008470:Meconium / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; C508606:CXCL8 protein, human; C406407:DEFB1 protein, human; C106641:DEFB4A protein, human; D016209:Interleukin-8; C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96; D008840:Microfilament Proteins; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C569754:VIL1 protein, human; D023083:beta-Defensins