Hepatic inflammatory mediators contribute to intestinal damage in necrotizing enterocolitis

MD Halpern, H Holubec… - American Journal …, 2003 - journals.physiology.org
MD Halpern, H Holubec, JA Dominguez, YG Meza, CS Williams, MC Ruth, RS McCuskey…
American Journal of Physiology-Gastrointestinal and Liver …, 2003journals.physiology.org
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 …
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.
American Physiological Society