IL-1 receptor blockade prevents fetal cortical brain injury but not preterm birth in a mouse model of inflammation-induced preterm birth and perinatal brain injury

Kirstin Leitner, Mofeedah Al Shammary, Michael Mclane, Michael V. Johnston, Michal A. Elovitz, Irina Burd

Research output: Contribution to journalArticle

Abstract

Problem: Exposure to intrauterine inflammation, associated with preterm birth, has been linked to a devastating spectrum of neurobehavioral disorders. Mechanisms of this injury are unknown. Using a mouse model of intrauterine inflammation, we have observed a disruption of fetal neuronal morphology along with a marked elevation of interleukin (IL)-1β in the fetal brain and placenta. In this study, we hypothesized that IL-1 plays a key role in perinatal brain injury. Method of study: Utilizing a mouse model of inflammation-induced preterm birth, we investigated the role of IL-1 in fetal cortical injury as well as preterm birth. In these studies, dams received systemic treatment with IL-1 receptor antagonist prior to administration of intrauterine inflammation. Results: Systemic maternal antagonism of IL-1 improved fetal cortical neuronal injury associated with the exposure to intrauterine inflammation, without affecting the phenotype of preterm birth. IL-1 receptor antagonist blocked activation of neuronal nitric oxide synthase in perinatal cortex, a key enzyme implicated in neurotoxicity. Conclusion: Our data suggest that fetal cortical brain injury and preterm birth may occur by divergent mechanisms. Furthermore, our studies indicate maternal administration of IL-1 receptor antagonist (IL-1RA) blocked neuronal nitric oxide synthase activation observed in the brain cortex and, we speculate, that this alteration in activation leads to demonstrated decreased neurotoxicity.

Original languageEnglish (US)
Pages (from-to)418-426
Number of pages9
JournalAmerican Journal of Reproductive Immunology
Volume71
Issue number5
DOIs
StatePublished - May 2014

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Keywords

  • IL-1 receptor antagonist
  • Intrauterine inflammation
  • Mouse model

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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