Selective IL-1α exposure to the fetal gut, lung, and chorioamnion/skin causes intestinal inflammatory and developmental changes in fetal sheep

M Nikiforou, Matthew Kemp, R. Van Gorp, Masatoshi Saito, John Newnham, N Reynaert, L. Janssen, Alan Jobe, Suhas Kallapur, Boris Kramer, T.G.M. Wolfs

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

© 2016 USCAP, Inc. Chorioamnionitis, caused by intra-amniotic exposure to bacteria and their toxic components, is associated with fetal gut inflammation and mucosal injury. In a translational ovine model, we have shown that these adverse intestinal outcomes to chorioamnionitis were the combined result of local gut and pulmonary-driven systemic immune responses. Chorioamnionitis-induced gut inflammation and injury was largely prevented by inhibiting interleukin-1 (IL-1) signaling. Therefore, we investigated whether local (gut-derived) IL-1α signaling or systemic IL-1α-driven immune responses (lung or chorioamnion/skin-derived) were sufficient for intestinal inflammation and mucosal injury in the course of chorioamnionitis. Fetal surgery was performed in sheep to isolate the lung, gastrointestinal tract, and chorioamnion/skin, and IL-1α or saline was given into the trachea, stomach, or amniotic cavity 1 or 6 days before preterm delivery. Selective IL-1α exposure to the lung, gut, or chorioamnion/skin increased the CD3+ cell numbers in the fetal gut. Direct IL-1α exposure to the gut impaired intestinal zonula occludens protein-1 expression, induced villus atrophy, changed the expression pattern of intestinal fatty acid-binding protein along the villus, and increased the CD68, IL-1, and TNF-α mRNA levels in the fetal ileum. With lung or chorioamnion/skin exposure to IL-1α, intestinal inflammation was associated with increased numbers of blood leukocytes without induction of intestinal injury or immaturity. We concluded that local IL-1α signaling was required for intestinal inflammation, disturbed gut maturation, and mucosal injury in the context of chorioamnionitis.
Original languageEnglish
Pages (from-to)69-80
JournalLaboratory Investigation
Volume96
Issue number1
DOIs
Publication statusPublished - 2016

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