IL-1α Mediated Chorioamnionitis Induces Depletion of FoxP3+Cells and Ileal Inflammation in the Ovine Fetal Gut

Background: Endotoxin induced chorioamnionitis increases IL-1 and provokes an inflammatory response in the fetal ileum that interferes with intestinal maturation. In the present study, we tested in an ovine chorioamnionitis model whether IL-1 is a major cytokine driving the inflammatory response in the fetal ileum. Method: Sheep bearing singleton fetuses received a single intraamniotic injection of recombinant ovine IL-1 alpha at 7, 3 or 1 d before caesarian delivery at 125 days gestational age (term = 150 days). Results: 3 and 7 d after IL-1 alpha administration, intestinal mRNA levels for IL-4, IL-10, IFN-gamma and TNF-alpha were strongly elevated. Numbers of CD3+ and CD4+ T-lymphocytes and myeloidperoxidase+ cells were increased whereas FoxP3+ T-cells were detected at low frequency. This increased proinflammatory state was associated with ileal mucosal barrier loss as demonstrated by decreased levels of the intestinal fatty acid binding protein and disruption of the tight junctional protein ZO-1. Conclusion: Intraamniotic IL-1 alpha causes an acute detrimental inflammatory response in the ileum, suggesting that induction of IL-1 is a critical element in the pathophysiological effects of endotoxin induced chorioamnionitis. A disturbed balance between T-effector and FoxP3+ cells may contribute to this process.