Antenatal IL-1-dependent inflammation persists postnatally and causes retinal and sub-retinal vasculopathy in progeny

Sci Rep. 2018 Aug 8;8(1):11875. doi: 10.1038/s41598-018-30087-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chorioamnionitis / metabolism
  • Choroid / metabolism
  • Disease Models, Animal
  • Female
  • Hyperoxia / metabolism
  • Inflammation / metabolism*
  • Interleukin 1 Receptor Antagonist Protein / metabolism
  • Interleukin-1beta / metabolism*
  • Mice
  • Pregnancy
  • Receptors, Interleukin-1 / metabolism
  • Retina / metabolism*
  • Retinal Diseases / metabolism*
  • Retinal Vessels / metabolism*


  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Receptors, Interleukin-1

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