Antenatal ureaplasma infection impairs development of the fetal ovine gut in an IL-1-dependent manner

1] Department of Neonatology, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio, USA [2] Department of Pediatrics, Maastricht University Medical Center (MUMC), School of Oncology and Developmental Biology (GROW), Maastricht, The Netherlands.
Mucosal Immunology (Impact Factor: 7.37). 11/2012; 6(3). DOI: 10.1038/mi.2012.97
Source: PubMed


Ureaplasma infection of the amniotic cavity is associated with adverse postnatal intestinal outcomes. We tested whether interleukin-1 (IL-1) signaling underlies intestinal pathology following ureaplasma exposure in fetal sheep. Pregnant ewes received intra-amniotic injections of ureaplasma or culture media for controls at 3, 7, and 14 d before preterm delivery at 124 d gestation (term 150 d). Intra-amniotic injections of recombinant human interleukin IL-1 receptor antagonist (rhIL-1ra) or saline for controls  were given 3 h before and every 2 d after Ureaplasma injection. Ureaplasma exposure caused fetal gut inflammation within 7 d with damaged villus epithelium and gut barrier loss. Proliferation, differentiation, and maturation of enterocytes were significantly reduced after 7 d of ureaplasma exposure, leading to severe villus atrophy at 14 d. Inflammation, impaired development and villus atrophy of the fetal gut was largely prevented by intra-uterine rhIL-1ra treatment. These data form the basis for a clinical understanding of the role of ureaplasma in postnatal intestinal pathologies.Mucosal Immunology advance online publication 14 November 2012; doi:10.1038/mi.2012.97.

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