Hepatic inflammatory mediators contribute to intestinal damage in necrotizing enterocolitis.
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 multisystem 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-alpha, and inducible nitric oxide synthase were evaluated. Intestinal luminal TNF-alpha levels were also measured. Production of hepatic IL-18 and TNF-alpha 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-alpha 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.
Halpern
Melissa D
MD
Department of Pediatrics and Steele Memorial Children's Research Center, University of Arizona, Tucson, Arizona 85724, USA. mhalpern@peds.arizona.edu
Holubec
Hana
H
Dominguez
Jessica A
JA
Meza
Yolanda G
YG
Williams
Catherine S
CS
Ruth
Miriam C
MC
McCuskey
Robert S
RS
Dvorak
Bohuslav
B
D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000276:immunology; D003080:Cold Temperature; D004750:Enteral Nutrition; D020345:Enterocolitis, Necrotizing / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D015870:Gene Expression / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism*; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D007422:Intestines / Q000276:immunology; D007728:Kupffer Cells / Q000473:pathology; D008099:Liver / Q000276:immunology* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D018836:Inflammation Mediators; D020382:Interleukin-18; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat