IL-1 receptor antagonist protects against placental and neurodevelopmental defects induced by maternal inflammation.
The precise role of maternal bacterial infection and inflammation occurring at the end of gestation is a controversial matter. Although it is recognized as an independent risk factor for neurodevelopmental diseases such as cerebral palsy, mental deficiency, and autism, it remains unclear whether it is causal or simply associated with the diseases. In this study, we demonstrate that IL-1 plays a key role in mediating severe placental damage and neurodevelopmental anomalies in offspring. Our results show that end of gestation exposure of pregnant rats to systemic microbial product (LPS) triggers placental inflammation and massive cell death, fetal mortality, and both forebrain white matter and motor behavioral alterations in the offspring. All these effects are alleviated by the coadministration of IL-1 receptor antagonist with LPS, suggesting a possible protective treatment against human placental and fetal brain damage.
Girard
Sylvie
S
Laboratoire de Neurologie Pédiatrique, Département de Pédiatrie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Tremblay
Luc
L
Lepage
Martin
M
Sébire
Guillaume
G
D000818:Animals; D001927:Brain Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008279:Magnetic Resonance Imaging; D010922:Placenta Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*
D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1