title: Mucosal loss with increased expression of IL-6, IL-8, and COX-2 in a formula-feeding only neonatal rat model of necrotizing enterocolitis.
abstract: BACKGROUND
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatric Surgery, UKE: University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Electronic address: r.bergholz@uke.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Bergholz
authors.forename: Marcus
authors.initials: M
authors.lastname: Zschiegner
authors.forename: Georg
authors.initials: G
authors.lastname: Eschenburg
authors.forename: Katharina
authors.initials: K
authors.lastname: Wenke
authors.forename: Bastian
authors.initials: B
authors.lastname: Tiemann
authors.forename: Beate
authors.initials: B
authors.lastname: Roth
authors.forename: Birgit
authors.initials: B
authors.lastname: Appl
authors.forename: Konrad
authors.initials: K
authors.lastname: Reinshagen
authors.forename: Dirk
authors.initials: D
authors.lastname: Sommerfeldt
authors.forename: Ina
authors.initials: I
authors.lastname: Ridderbusch
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D007082:Ileum / Q000378:metabolism; D007223:Infant; D041943:Infant Formula / Q000494:pharmacology*; D007249:Inflammation; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D008892:Milk; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat
keywords: Animal model; COX-2; Enterocolitis; IL-6; IL-8; Necrotizing; Surgery