Back to Search Start Over

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

Authors :
Nikiforou, Maria
Kemp, Matthew W
van Gorp, Rick H
Saito, Masatoshi
Newnham, John P
Reynaert, Niki L
Janssen, Leon E W
Jobe, Alan H
Kallapur, Suhas G
Kramer, Boris W
Wolfs, Tim G A M
Source :
Laboratory Investigation; January 2016, Vol. 96 Issue: 1 p69-80, 12p
Publication Year :
2016

Abstract

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-1αsignaling 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-1αor saline was given into the trachea, stomach, or amniotic cavity 1 or 6 days before preterm delivery. Selective IL-1αexposure to the lung, gut, or chorioamnion/skin increased the CD3+ cell numbers in the fetal gut. Direct IL-1αexposure 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-αmRNA 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-1αsignaling was required for intestinal inflammation, disturbed gut maturation, and mucosal injury in the context of chorioamnionitis.

Details

Language :
English
ISSN :
00236837 and 15300307
Volume :
96
Issue :
1
Database :
Supplemental Index
Journal :
Laboratory Investigation
Publication Type :
Periodical
Accession number :
ejs62074013
Full Text :
https://doi.org/10.1038/labinvest.2015.127