Mucosal loss with increased expression of IL-6, IL-8, and COX-2 in a formula-feeding only neonatal rat model of necrotizing enterocolitis

• Published in: Journal of pediatric surgery 2013-11, Vol.48 (11), p.2301-2307
• Main Authors: Bergholz, Robert, Zschiegner, Marcus, Eschenburg, Georg, Wenke, Katharina, Tiemann, Bastian, Roth, Beate, Appl, Birgit, Reinshagen, Konrad, Sommerfeldt, Dirk, Ridderbusch, Ina
• Format: Article
• Language: English
• Subjects: Animal model; Animals; Animals, Newborn; Body Weight; COX-2; Cyclooxygenase 2 - biosynthesis; Cyclooxygenase 2 - genetics; Disease Models, Animal; Enterocolitis; Enterocolitis, Necrotizing - metabolism; Enterocolitis, Necrotizing - surgery; Humans; IL-6; IL-8; Ileum - metabolism; Infant; Infant Formula - pharmacology; Inflammation; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Interleukin-8 - biosynthesis; Interleukin-8 - genetics; Intestinal Mucosa - metabolism; Milk; Necrotizing; Pediatrics; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Surgery; Time Factors
• ISSN: 0022-3468; 1531-5037
• DOI: 10.1016/j.jpedsurg.2013.04.028

Abstract Introduction The aim of our study is to establish a reliable neonatal rat model by formula feeding only for evaluation of early surgical intervention on the course of experimental necrotizing enterocolitis (NEC). Material and methods Newborn Sprague–Dawley rats were divided into 50 breast-fed (group 1) and 38 formula fed (Similac/Esbilac, group 2) animals. The pups were sacrificed on the 4th, 5th, and 6th day of life and the terminal intestine examined for macroscopic and histologic changes as well as cytokine expression. Results The histological mucosal damage was significantly higher of group 2 compared to group 1. The area of the vital mucosa of group 2 was significantly (58.57%, p < 0.001) lower compared to group 1 (75.12%). The mRNA expression of the inflammatory cytokines IL-6, IL-8 and COX-2 was significantly 2-, 5- and 10-fold increased in group 2 compared to group 1. Discussion Formula fed newborn rats displayed an inflammatory enterocolitis similar to human NEC. Our study demonstrates a significant loss of mucosa in animals with NEC having increased expression levels of IL-6, IL-8 and COX-2. Mucosal loss appears to be a distinct feature of experimental NEC and has to be correlated with the human disease.