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Type: Journal article
Title: Antenatal IL-1-dependent inflammation persists postnatally and causes retinal and sub-retinal vasculopathy in progeny
Author: Beaudry-Richard, A.
Nadeau-Vallée, M.
Prairie, É.
Maurice, N.
Heckel, É.
Nezhady, M.
Pundir, S.
Madaan, A.
Boudreault, A.
Hou, X.
Quiniou, C.
Sierra, E.
Beaulac, A.
Lodygensky, G.
Robertson, S.
Keelan, J.
Adams-Waldorf, K.
Olson, D.
Rivera, J.
Lubell, W.
et al.
Citation: Scientific Reports, 2018; 8(1):11875-1-11875-13
Publisher: Nature Publishing Group
Issue Date: 2018
ISSN: 2045-2322
Statement of
Alexandra Beaudry-Richard, Mathieu Nadeau-Vallée, Élizabeth Prairie, Noémie Maurice ... Sarah A. Robertson ... David M. Olson ... et al.
Abstract: Antenatal inflammation as seen with chorioamnionitis is harmful to foetal/neonatal organ development including to eyes. Although the major pro-inflammatory cytokine IL-1β participates in retinopathy induced by hyperoxia (a predisposing factor to retinopathy of prematurity), the specific role of antenatal IL-1β associated with preterm birth (PTB) in retinal vasculopathy (independent of hyperoxia) is unknown. Using a murine model of PTB induced with IL-1β injection in utero, we studied consequent retinal and choroidal vascular development; in this process we evaluated the efficacy of IL-1R antagonists. Eyes of foetuses exposed only to IL-1β displayed high levels of pro-inflammatory genes, and a persistent postnatal infiltration of inflammatory cells. This prolonged inflammatory response was associated with: (1) a marked delay in retinal vessel growth; (2) long-lasting thinning of the choroid; and (3) long-term morphological and functional alterations of the retina. Antenatal administration of IL-1R antagonists - 101.10 (a modulator of IL-1R) more so than Kineret (competitive IL-1R antagonist) - prevented all deleterious effects of inflammation. This study unveils a key role for IL-1β, a major mediator of chorioamnionitis, in causing sustained ocular inflammation and perinatal vascular eye injury, and highlights the efficacy of antenatal 101.10 to suppress deleterious inflammation.
Keywords: Interleukins; paediatric research; retinopathy of prematurity; target identification; translational research
Rights: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
DOI: 10.1038/s41598-018-30087-4
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