Abstract
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.
Conclusion:
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.
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Acknowledgements
The authors thank Claudia Foerster as well as Silvia Vogel (technicians) for their excellent technical support. hBD2 antibodies were kindly donated by Tomas Ganz (UCLA). All authors contributed significantly to this work: A.C.W.J. and J.P. were involved in study design, experimental analysis, coordination, and data interpretation. M.Z. and S.W. were involved in study design, coordination, and data interpretation.
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Jenke, A., Zilbauer, M., Postberg, J. et al. Human β-defensin 2 expression in ELBW infants with severe necrotizing enterocolitis. Pediatr Res 72, 513–520 (2012). https://doi.org/10.1038/pr.2012.110
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DOI: https://doi.org/10.1038/pr.2012.110
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