Premature birth is a common and critical health issue in fetal-maternal medicine with long-term consequences especially for early preterm neonates. The pathophysiology of preterm labour is poorly understood and the causal factors uncertain, but inflammatory mechanisms are clearly implicated. Toll-like receptors (TLRs) are critical upstream gate-keepers controlling the inflammatory activation that precedes preterm delivery and pro-inflammatory cytokine interleukin-1 beta (IL-1b) has been identified as a major upstream product following the activation of the TLR pathway. Group B Streptococcus (GBS) or Streptococcus agalactiae is a gram-positive bacteria and a TLR2/TLR8 ligand, is considered to be a leading cause in neonatal sepsis following preterm birth. Previously we have shown that inhibition of IL-1 signaling using rytvela, a non-competitive allosteric peptide inhibitor of IL-1 receptor (IL-1R) signaling, can reduce GBS-induced preterm birth in mice by 50% and improves neonatal survival rates. This project seeks to investigate whether inhibition of IL-1 signaling using the IL-1R antagonist rytvela may prevent the parturition cascade caused by GBS-induced inflammation. Pregnant C57Bl/6 mice were administered intrauterine heat-killed GBS (5x109 IU/100 µl) or PBS, with or without co-administration of rytvela (ip), on gestational day (GD) 16.5 and were killed 4 hours later for RT-PCR analysis of inflammatory cytokines in gestational tissues adjacent to the GBS injection site (n=2 samples from 6-8 dams per group). Administration of rytvela was found to suppress GBS-induced expression of Il1b, Ifng, Ptgs2, Il10 and Il18 expression in the uterus. These results demonstrate that intervention with rytvela to suppress the IL-1-induced inflammatory cascade can mitigate GBS-induced preterm delivery by preventing premature activation of uterine activation proteins and subsequent onset of labour in mice. The data support continued investigation of the IL-1 pathway as a potential target for new prevention or treatment options in women at risk of infection-associated preterm delivery.