ArticleEMBO molecular medicine2025
A novel modulator of IL-6R prevents inflammation-induced preterm birth and improves newborn outcome.
Article in EMBO molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Inflammatory Stress Response During Pregnancy as a Connecting Link in Intergenerational Risk Cascades.Developmental psychobiology · 2026Article
- Treg cells retain stable lineage commitment during pregnancy in mice after late gestation inflammatory challenge.Immunology and cell biology · 2026Article
- Neuroinflammatory mechanisms and pharmacological advances in autism spectrum disorder: from inflammatory pathways to targeted interventions.Frontiers in immunology · 2026Review
- Single-cell-level digital twins for preterm birth prevention strategies.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
30 authors.
Funding
Abstract
Preterm birth (PTB) is a major cause of neonatal mortality and morbidity. Evidence supports a determinant role for interleukin-6 (IL-6) in the pathophysiology of PTB. Our group developed a small peptide, HSJ633, that antagonizes the interleukin-6 receptor (IL-6R). Binding assays performed on HEK-Blue IL-6 cells reveal that HSJ633 appears to bind to IL-6R on a site remote from the IL-6 binding domain. Concordantly, HSJ633 selectively inhibits STAT3 phosphorylation while preserving the activation of cytoprotective AKT, p38, and ERK 1/2. In vivo, in a murine model of LPS-induced PTB, HSJ633 reduces inflammation in gestational and fetal tissues, preserves the integrity of fetal organs, and improves the survival of neonatal progeny when administered before and after the induction of labor by an inflammatory stimulus. Relevantly, the pharmacological inhibition of STAT3 in mice is sufficient to prevent PTB. Findings reveal first-in-class efficacy of a small peptide inhibitor of IL-6R, namely HSJ633, in impeding the inflammatory cascade associated with PTB and mitigating adverse neonatal outcomes.
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