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
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U2 - 10.1152/ajpgi.00353.2002
DO - 10.1152/ajpgi.00353.2002
M3 - Article
C2 - 12529262
AN - SCOPUS:0345549530
SN - 0193-1857
VL - 284
SP - G695-G702
JO - American Journal of Physiology - Gastrointestinal and Liver Physiology
JF - American Journal of Physiology - Gastrointestinal and Liver Physiology
IS - 4 47-4
ER -