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
Article first published online: 5 MAR 2014
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
American Journal of Reproductive Immunology
Volume 71, Issue 5, pages 418–426, May 2014
How to Cite
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. Am J Reprod Immunol 2014; 71: 418–426, , , , , .
- Issue published online: 16 APR 2014
- Article first published online: 5 MAR 2014
- Manuscript Accepted: 17 JAN 2014
- Manuscript Received: 11 DEC 2013
- NICHD. Grant Number: K08HD073315
- Passano Foundation
- IL-1 receptor antagonist;
- intrauterine inflammation;
- mouse model
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.
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.
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.