Hepatic inflammatory mediators contribute to intestinal damage in necrotizing enterocolitis

Melissa D Halpern, Hana Holubec, Jessica A. Dominguez, Yolanda G. Meza, Catherine S. Williams, Miriam C. Ruth, Robert S. McCuskey, Bohuslav Dvorak

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal disease of premature infants. Along with pathological effects in the ileum, severe NEC is often accompanied by mutisystem organ failure, including liver failure. The aim of this study was to determine the changes in hepatic cytokines and inflammatory mediators in experimental NEC. The well-established neonatal rat model of NEC was used in this study, and changes in liver morphology, numbers of Kupffer cells (KC), gene expression, and histological localization of IL-18, TNF-α, and inducible nitric oxide synthase were evaluated. Intestinal luminal TNF-α levels were also measured. Production of hepatic IL-18 and TNF-α and numbers of KC were increased in rats with NEC and correlated with the progression of intestinal damage during NEC development. Furthermore, increased levels of TNF-α in the intestinal lumen of rats with NEC was significantly decreased when KC were inhibited with gadolinium chloride. These results suggest an important role of the liver and the gut-liver axis in NEC pathogenesis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume284
Issue number4 47-4
StatePublished - Apr 1 2003

Fingerprint

Necrotizing Enterocolitis
Liver
Kupffer Cells
Interleukin-18
Gastrointestinal Diseases
Liver Failure
Nitric Oxide Synthase Type II
Ileum
Premature Infants
Cytokines
Gene Expression

Keywords

  • Gastrointestinal system
  • Gut-liver axis
  • Inflammation
  • Neonatal

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Hepatic inflammatory mediators contribute to intestinal damage in necrotizing enterocolitis. / Halpern, Melissa D; Holubec, Hana; Dominguez, Jessica A.; Meza, Yolanda G.; Williams, Catherine S.; Ruth, Miriam C.; McCuskey, Robert S.; Dvorak, Bohuslav.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 284, No. 4 47-4, 01.04.2003.

Research output: Contribution to journalArticle

Halpern, MD, Holubec, H, Dominguez, JA, Meza, YG, Williams, CS, Ruth, MC, McCuskey, RS & Dvorak, B 2003, 'Hepatic inflammatory mediators contribute to intestinal damage in necrotizing enterocolitis', American Journal of Physiology - Gastrointestinal and Liver Physiology, vol. 284, no. 4 47-4.
Halpern, Melissa D ; Holubec, Hana ; Dominguez, Jessica A. ; Meza, Yolanda G. ; Williams, Catherine S. ; Ruth, Miriam C. ; McCuskey, Robert S. ; Dvorak, Bohuslav. / Hepatic inflammatory mediators contribute to intestinal damage in necrotizing enterocolitis. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2003 ; Vol. 284, No. 4 47-4.
@article{1ea75510d73141079cc35432c8049a96,
title = "Hepatic inflammatory mediators contribute to intestinal damage in necrotizing enterocolitis",
abstract = "Necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal disease of premature infants. Along with pathological effects in the ileum, severe NEC is often accompanied by mutisystem organ failure, including liver failure. The aim of this study was to determine the changes in hepatic cytokines and inflammatory mediators in experimental NEC. The well-established neonatal rat model of NEC was used in this study, and changes in liver morphology, numbers of Kupffer cells (KC), gene expression, and histological localization of IL-18, TNF-α, and inducible nitric oxide synthase were evaluated. Intestinal luminal TNF-α levels were also measured. Production of hepatic IL-18 and TNF-α and numbers of KC were increased in rats with NEC and correlated with the progression of intestinal damage during NEC development. Furthermore, increased levels of TNF-α in the intestinal lumen of rats with NEC was significantly decreased when KC were inhibited with gadolinium chloride. These results suggest an important role of the liver and the gut-liver axis in NEC pathogenesis.",
keywords = "Gastrointestinal system, Gut-liver axis, Inflammation, Neonatal",
author = "Halpern, {Melissa D} and Hana Holubec and Dominguez, {Jessica A.} and Meza, {Yolanda G.} and Williams, {Catherine S.} and Ruth, {Miriam C.} and McCuskey, {Robert S.} and Bohuslav Dvorak",
year = "2003",
month = "4",
day = "1",
language = "English (US)",
volume = "284",
journal = "American Journal of Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "4 47-4",

}

TY - JOUR

T1 - Hepatic inflammatory mediators contribute to intestinal damage in necrotizing enterocolitis

AU - Halpern, Melissa D

AU - Holubec, Hana

AU - Dominguez, Jessica A.

AU - Meza, Yolanda G.

AU - Williams, Catherine S.

AU - Ruth, Miriam C.

AU - McCuskey, Robert S.

AU - Dvorak, Bohuslav

PY - 2003/4/1

Y1 - 2003/4/1

N2 - Necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal disease of premature infants. Along with pathological effects in the ileum, severe NEC is often accompanied by mutisystem organ failure, including liver failure. The aim of this study was to determine the changes in hepatic cytokines and inflammatory mediators in experimental NEC. The well-established neonatal rat model of NEC was used in this study, and changes in liver morphology, numbers of Kupffer cells (KC), gene expression, and histological localization of IL-18, TNF-α, and inducible nitric oxide synthase were evaluated. Intestinal luminal TNF-α levels were also measured. Production of hepatic IL-18 and TNF-α and numbers of KC were increased in rats with NEC and correlated with the progression of intestinal damage during NEC development. Furthermore, increased levels of TNF-α in the intestinal lumen of rats with NEC was significantly decreased when KC were inhibited with gadolinium chloride. These results suggest an important role of the liver and the gut-liver axis in NEC pathogenesis.

AB - Necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal disease of premature infants. Along with pathological effects in the ileum, severe NEC is often accompanied by mutisystem organ failure, including liver failure. The aim of this study was to determine the changes in hepatic cytokines and inflammatory mediators in experimental NEC. The well-established neonatal rat model of NEC was used in this study, and changes in liver morphology, numbers of Kupffer cells (KC), gene expression, and histological localization of IL-18, TNF-α, and inducible nitric oxide synthase were evaluated. Intestinal luminal TNF-α levels were also measured. Production of hepatic IL-18 and TNF-α and numbers of KC were increased in rats with NEC and correlated with the progression of intestinal damage during NEC development. Furthermore, increased levels of TNF-α in the intestinal lumen of rats with NEC was significantly decreased when KC were inhibited with gadolinium chloride. These results suggest an important role of the liver and the gut-liver axis in NEC pathogenesis.

KW - Gastrointestinal system

KW - Gut-liver axis

KW - Inflammation

KW - Neonatal

UR - http://www.scopus.com/inward/record.url?scp=0345549530&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0345549530&partnerID=8YFLogxK

M3 - Article

C2 - 12529262

AN - SCOPUS:0345549530

VL - 284

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6143

IS - 4 47-4

ER -