Journal
FRONTIERS IN ENDOCRINOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2022.833121
Keywords
autism spectrum disorder (ASD); cerebral palsy (CP); fetal inflammatory response syndrome (FIRS); hyperactivity; interleukin-1 receptor antagonist; maternal immune activation; placentoprotection; neuroplacentology
Categories
Funding
- Canadian Institute of Health Research (CIHR) [6847]
- Program of Pharmacology, McGill University
- Research Institute of McGill University Health Center (RI MUHC)
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Group B Streptococcus (GBS) infection is a major risk factor for fetal organ injuries, preterm birth, and neurodevelopmental impairments. Blocking interleukin-1 (IL-1) can alleviate the inflammatory response and improve the weight gain of pregnant women.
Group B Streptococcus (GBS) is one of the most common bacteria isolated in human chorioamnionitis. Placental infection due to GBS is a major risk factor for fetal organ injuries, preterm birth, perinatal morbidity and mortality, and life-long multiorgan morbidities. Preclinical and clinical studies have shown that GBS-induced infection drives polymorphonuclear (PMN) cell infiltration within the placenta, the hallmark of human chorioamnionitis. In preclinical and clinical studies, the upregulation of interleukin(IL)-1 beta in the placenta and maternal/fetal blood was associated with a high risk of neurodevelopmental impairments in the progeny. We hypothesized that targeted IL-1 blockade administered to the dam alleviates GBS-induced chorioamnionitis and the downstream fetal inflammatory response syndrome (FIRS). IL-1 receptor antagonist (IL-1Ra) improved the gestational weight gain of GBS-infected dams and did not worsen the infectious manifestations. IL-1Ra reduced the IL-1 beta titer in the maternal sera of GBS-infected dams. IL-1Ra decreased the levels of IL-1 beta, IL-6, chemokine (C-X-C motif) ligand 1 (CXCL1), and polymorphonuclear (PMN) infiltration in GBS-infected placenta. IL-1Ra treatment reduced the IL-1 beta titer in the fetal sera of GBS-exposed fetuses. IL-1 blockade also alleviated GBS-induced FIRS and subsequent neurobehavioral impairments of the offspring without worsening the outcome of GBS infection. Altogether, these results showed that IL-1 plays a key role in the physiopathology of live GBS-induced chorioamnionitis and consequent neurobehavioral impairments.
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