Chorioamnionitis Induced Hepatic Inflammation and Disturbed Lipid Metabolism in Fetal Sheep

Abstract

Chorioamnionitis frequently induces a fetal inflammatory response syndrome (FIRS), characterized by an elevation of proinflammatory mediators and systemic inflammation. Although there is increasing evidence that inflammation and lipid metabolism influence each other, the effects of chorioamnionitis-induced FIRS on fetal lipid homeostasis are currently not known. Accordingly, we hypothesize that chorioamnionitis induces an inflammatory response in the fetal liver, consequently leading to metabolic disturbances. Chorioamnionitis was induced by intra-amniotic injection of 10 mg endotoxin (control) for 2 d or 2 wk before delivery. Saline injections were given to controls. The effect of chorioamnionitis on hepatic inflammation and metabolic parameters was analyzed in ovine fetuses at the GA of 125 d (normal GA ϭ 150 d). We found that 2 d after the endotoxin injections, inflammatory markers were significantly higher compared with controls. In addition, lipid and glucose metabolism were disturbed in response to endotoxin. Moreover, the antioxidant state capacity was reduced, and hepatic damage was apparent. Two weeks after the endotoxin injections, the fetal livers were still inflamed and had higher glucose concentrations in the blood. In addition, the levels of markers for hepatic damage (alanine aminotransferase and aspartate aminotransferase) were increased. In conclusion, chorioamnionitis induces liver inflammation leading to metabolic disturbances in the fetus. (Pediatr Res 68: 466-472, 2010)

Responses of the spleen to intraamniotic lipopolysaccharide exposure in fetal sheep

“…This splenic inflammatory response may contribute to the multiorgan inflammation and injury after IA inflammation by persistent production of proinflammatory cytokines and activated immune cells into the systemic circulation. We have reported sustained inflammation in the lungs (13), gut (14), liver (15), and brain (16) of animals exposed to IA LPS up to 15 d after administration. Persistent tissue inflammation was accompanied by lung injury and delayed alveolar development (17), mucosal damage, villus atrophy, and impaired development in the gut (14,18) and white matter injury in the brain (16), which are all clinical hallmarks of adverse neonatal outcomes.…”

Repeated exposure to intra-amniotic LPS partially protects against adverse effects of intravenous LPS in preterm lambs

“…The effects of chorioamnionitis on the fetal liver surprisingly showed persistence of inflammatory and metabolic changes for months in sheep. [38][39][40] Our previous studies demonstrated that blood monocytes from preterm lambs exposed to two doses of i.a. LPS were refractory to LPS challenge in vitro.…”

S100A8/A9 modulates inflammatory collateral tissue damage during intraperitoneal origin systemic candidiasis

“…Histological preparations and inflammatory score analyses were conducted as in previous reports (15,30). For the inflammatory score, Whole sections were analyzed for inflammation and scored under the supervision of a specialized animal pathologist.…”

“…For the inflammatory score, Whole sections were analyzed for inflammation and scored under the supervision of a specialized animal pathologist. The sections from each animal were scored as zero if they had no inflammatory cells present in the tissue, one for a few inflammatory cells (1–20 cells), two for moderate cell infiltration (21–40 cells), three for a large number of inflammatory cells (41–60 cells), and four if inflammation was spread all over in the tissue (61 cells) (30).…”