Maternal milk reduces severity of necrotizing enterocolitis and increases intestinal IL-10 in a neonatal rat model

Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Maternal milk has been suggested to be partially protective against NEC; however, the mechanisms of this protection are not defined. The aim of this study was to examine the effect(s) of artificial feeding of r...

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Published inPediatric research Vol. 53; no. 3; pp. 426 - 433
Main Authors DVORAK, Bohuslav, HALPERN, Melissa D, HOLUBEC, Hana, DVORAKOVA, Katerina, DOMINGUEZ, Jessica A, WILLIAMS, Catherine S, MEZA, Yolanda G, KOZAKOVA, Hana, MCCUSKEY, Robert S
Format Journal Article
LanguageEnglish
Published Hagerstown, MD Lippincott Williams & Wilkins 01.03.2003
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Abstract Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Maternal milk has been suggested to be partially protective against NEC; however, the mechanisms of this protection are not defined. The aim of this study was to examine the effect(s) of artificial feeding of rat milk (RM)-versus cow milk-based rat milk substitute (RMS) on the development of NEC in a neonatal rat model and elucidate the role of inflammatory cytokines in NEC pathogenesis. Newborn rats were artificially fed with either collected RM or RMS. Experimental NEC was induced by exposure to asphyxia and cold stress and evaluated by histologic scoring of damage in ileum. Intestinal cytokine mRNA expression was determined by real-time PCR. Cytokine histologic localization was performed by confocal microscopy. Similar to human NEC, artificial feeding of RM reduces the incidence and severity of NEC injury in neonatal rats. Freezing and thawing of collected RM did not eliminate the protective effect of maternal milk. Ileal IL-10 expression was significantly increased in the RM group compared with RMS. Increased IL-10 peptide production was detected in the RM group with signal localized predominantly in the cytoplasm of villus epithelial cells. These results suggest that the protective effect of maternal milk is associated with increased production of anti-inflammatory IL-10 in the site of injury. Better understanding of the mechanisms underlying these protective effects could be beneficial either in the prevention of NEC or in the development of future therapeutic strategies to cure NEC.
AbstractList Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Maternal milk has been suggested to be partially protective against NEC; however, the mechanisms of this protection are not defined. The aim of this study was to examine the effect(s) of artificial feeding of rat milk (RM)-versus cow milk-based rat milk substitute (RMS) on the development of NEC in a neonatal rat model and elucidate the role of inflammatory cytokines in NEC pathogenesis. Newborn rats were artificially fed with either collected RM or RMS. Experimental NEC was induced by exposure to asphyxia and cold stress and evaluated by histologic scoring of damage in ileum. Intestinal cytokine mRNA expression was determined by real-time PCR. Cytokine histologic localization was performed by confocal microscopy. Similar to human NEC, artificial feeding of RM reduces the incidence and severity of NEC injury in neonatal rats. Freezing and thawing of collected RM did not eliminate the protective effect of maternal milk. Ileal IL-10 expression was significantly increased in the RM group compared with RMS. Increased IL-10 peptide production was detected in the RM group with signal localized predominantly in the cytoplasm of villus epithelial cells. These results suggest that the protective effect of maternal milk is associated with increased production of anti-inflammatory IL-10 in the site of injury. Better understanding of the mechanisms underlying these protective effects could be beneficial either in the prevention of NEC or in the development of future therapeutic strategies to cure NEC.
Author HALPERN, Melissa D
MCCUSKEY, Robert S
WILLIAMS, Catherine S
HOLUBEC, Hana
MEZA, Yolanda G
DVORAK, Bohuslav
DOMINGUEZ, Jessica A
DVORAKOVA, Katerina
KOZAKOVA, Hana
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  surname: DVORAK
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  organization: Department of Pediatrics and Steele Memorial Children's Research Center, University of Arizona, Tucson, Arizona 85724, United States
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  givenname: Melissa D
  surname: HALPERN
  fullname: HALPERN, Melissa D
  organization: Department of Pediatrics and Steele Memorial Children's Research Center, University of Arizona, Tucson, Arizona 85724, United States
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  givenname: Hana
  surname: HOLUBEC
  fullname: HOLUBEC, Hana
  organization: Department of Microbiology & Immunology, University of Arizona, Tucson, Arizona 85724, United States
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  givenname: Katerina
  surname: DVORAKOVA
  fullname: DVORAKOVA, Katerina
  organization: Department of Microbiology & Immunology, University of Arizona, Tucson, Arizona 85724, United States
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  givenname: Jessica A
  surname: DOMINGUEZ
  fullname: DOMINGUEZ, Jessica A
  organization: Department of Pediatrics and Steele Memorial Children's Research Center, University of Arizona, Tucson, Arizona 85724, United States
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  givenname: Catherine S
  surname: WILLIAMS
  fullname: WILLIAMS, Catherine S
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  givenname: Yolanda G
  surname: MEZA
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  organization: Department of Pediatrics and Steele Memorial Children's Research Center, University of Arizona, Tucson, Arizona 85724, United States
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  surname: MCCUSKEY
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  organization: Department of Pediatrics and Steele Memorial Children's Research Center, University of Arizona, Tucson, Arizona 85724, United States
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Issue 3
Keywords Vertebrata
Mammalia
Rat
Newborn animal
Rodentia
Interleukin 10
Digestive diseases
Intestinal disease
Necrotizing enterocolitis
Mechanism of action
Protection
Breast milk
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PublicationTitle Pediatric research
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Snippet Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Maternal milk has been suggested to be partially protective against...
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SubjectTerms Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Animals, Newborn
Asphyxia - immunology
Asphyxia - metabolism
Biological and medical sciences
Cold Temperature
Disease Models, Animal
Emergency and intensive care: neonates and children. Prematurity. Sudden death
Enteral Nutrition
Enterocolitis, Necrotizing - diet therapy
Enterocolitis, Necrotizing - epidemiology
Enterocolitis, Necrotizing - immunology
Female
Ileum - immunology
Ileum - metabolism
Ileum - ultrastructure
Incidence
Intensive care medicine
Interleukin-10 - metabolism
Intestinal Mucosa - immunology
Intestinal Mucosa - metabolism
Intestinal Mucosa - ultrastructure
Medical sciences
Microscopy, Electron, Scanning
Milk
Rats
Rats, Sprague-Dawley
Severity of Illness Index
Stomach, duodenum, intestine, rectum, anus
Stress, Physiological - immunology
Stress, Physiological - metabolism
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Surgery of the digestive system
Weight Gain
Title Maternal milk reduces severity of necrotizing enterocolitis and increases intestinal IL-10 in a neonatal rat model
URI https://www.ncbi.nlm.nih.gov/pubmed/12595590
https://search.proquest.com/docview/73024720
Volume 53
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