IL1 blockade attenuates E. coli induced intrauterine inflammation and preterm labor in Rhesus macaques
Year: 2026
Type: preprint
Abstract: ABSTRACT Intrauterine infection and inflammation are major causes of preterm labor, yet antibiotics alone often fail to prevent preterm birth despite achieving microbial clearance. Interleukin1 (IL1) is a key mediator of intra-amniotic inflammation and functional progesterone withdrawal, processes linked to labor initiation. We tested whether IL1 blockade with the clinically approved IL1 receptor antagonist, anakinra, could reduce inflammation and preterm labor in a Rhesus macaque model of intra-amniotic Escherichia coli infection followed by delayed antibiotic treatment. Here we show that anakinra reduced the incidence of preterm labor by 40% (p=0.07), attenuated inflammation in the fetal membranes and cervix, and preserved progesterone receptor-B abundance in the fetal membranes. These effects were most pronounced in animals protected from preterm labor. Our findings in a relevant model support the translational potential of combining IL1 blockade with antibiotics for infection-associated preterm labor. One sentence summary Recombinant human IL1 receptor antagonist (anakinra) decreased E. coli infection induced preterm labor and partially decreased intrauterine inflammation in a non-human primate model of inflammation mediated preterm labor.
Authors: Pietro Presicce, Daniel Short, Monica Cappelletti, Natalia Perecki, Arne Gehlhaar, Alzbeta Godarova, Angela DeTomaso, Jacqueline Shauh, Liza Konnikova, Sivan Bercovici, Shiv Kale, Paul Babb, Lisa A. Miller, Sing Sing Way, William J. Zacharias, Hitesh Deshmukh, Senad Divanovic, Myung S. Sim, Alan H. Jobe, Claire A. Chougnet, Mark R. Johnson, Sam Mesiano, Suhas G. Kallapur
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7172482682