J Immunol. 2026 Feb 9;215(2):vkaf341. doi: 10.1093/jimmun/vkaf341.
ABSTRACT
Preterm birth is the leading cause of neonatal morbidity and mortality. Management of preterm labor relies on the use of tocolytics, like nifedipine, which fail to prevent preterm birth and related morbidities. Interleukin-1β plays significant roles in the pathophysiology of preterm birth including inflammation and uterine activation. The interleukin-1 allosteric receptor antagonist rytvela effectively suppresses inflammation and prevents preterm birth. We compared side-by-side rytvela and nifedipine in affecting preterm birth and offspring outcomes in a treatment modality approach. In a model of lipopolysaccharide-induced preterm birth, as of 2 hours post-lipopolysaccharide administration (peak inflammatory surge), pregnant CD-1 mice were treated with rytvela, nifedipine, or vehicle (water). Gestational tissues were collected to quantify inflammatory mediators. Neonatal integrity was evaluated through histological analysis of major organs. All datasets were analyzed by a one-way ANOVA or the Kruskal-Wallis test where appropriate and compared to the vehicle group. Preterm birth rates were assessed by a χ2 test. Unlike nifedipine, rytvela significantly decreased prematurity and mortality. Rytvela inhibited proinflammatory and uterine activation mediators in gestational tissues and improved neonatal outcomes, resulting in higher weight and length by day 7, and preserving lung, intestine, retinal, and brain microvascular integrity. Nifedipine failed to confer similar benefits. Administration of rytvela in a treatment mode after the onset of preterm labor curbed the inflammatory surge and mitigated adverse outcomes, surpassing the effects of nifedipine. Rytvela represents a promising treatment approach for preventing preterm birth complications and addressing this unmet medical need unfulfilled by current tocolytics.
PMID:41729165 | DOI:10.1093/jimmun/vkaf341