Inhibition of interleukin-1 signaling protects against Group B Streptococcus-induced preterm birth and fetal loss in mice

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dc.contributor.authorChin, P.Y.
dc.contributor.authorMoldenhauer, L.M.
dc.contributor.authorLubell, W.D.
dc.contributor.authorOlson, D.M.
dc.contributor.authorChemtob, S.
dc.contributor.authorKeelan, J.A.
dc.contributor.authorRobertson, S.A.
dc.date.issued2025
dc.description.abstractGroup B streptococcus is a common microbial agent associated with spontaneous preterm birth and fetal inflammatory response syndrome. In this study, we evaluated the utility of rytvela, a novel peptide antagonist of the interleukin-1 receptor, to suppress inflammatory activation, prolong gestation and improve neonatal outcomes induced in mice by Group B streptococcus. Pregnant mice were administered rytvela or PBS on gestation day 16.5, immediately prior and following surgical administration of heat-killed Group B streptococcus (hkGBS) or PBS into the uterine cavity. Treatment with rytvela prevented preterm delivery and alleviated fetal demise in utero and in the perinatal phase elicited by hkGBS. Compared to pups exposed to hkGBS alone, pups of dams co-administered rytvela exhibited substantially improved survival and growth through to weaning. Analysis by qPCR showed expression of inflammatory cytokine genes Il1b, Il6, Tnf, and Ifng in uterine tissues, and Il1b, Il6, and Tnf in fetal membranes, were stimulated by hkGBS and this increase was suppressed by co-administration of rytvela. Premature induction of uterine activation gene Ptgs2 in the myometrium was also attenuated by rytvela treatment. These data show that activation of IL1-mediated signaling in response to Group B streptococcus triggers an inflammatory cascade that causes preterm parturition and fetal inflammatory injury, and that rytvela can suppress inflammatory mediators to substantially improve pregnancy and fetal outcomes. Our findings add to accumulating evidence supporting clinical investigation of rytvela for fetal protection and delaying preterm birth.
dc.description.statementofresponsibilityPeck Y. Chin, Lachlan M. Moldenhauer, William D. Lubell, David M. Olson, Sylvain Chemtob, Jeffrey A. Keelan, Sarah A. Robertson
dc.identifier.citationJournal of Reproductive Immunology, 2025; 169:104520-1-104520-11
dc.identifier.doi10.1016/j.jri.2025.104520
dc.identifier.issn0165-0378
dc.identifier.issn1872-7603
dc.identifier.orcidChin, P.Y. [0000-0002-0923-0553]
dc.identifier.orcidMoldenhauer, L.M. [0000-0002-3141-2521]
dc.identifier.orcidRobertson, S.A. [0000-0002-9967-0084]
dc.identifier.urihttps://hdl.handle.net/2440/146302
dc.language.isoen
dc.publisherElsevier
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1198172
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1145295
dc.rights© 2025 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
dc.source.urihttps://doi.org/10.1016/j.jri.2025.104520
dc.subjectpreterm labor; pregnancy; fetal growth; postnatal outcomes; interleukin-1; cytokines; inflammation; GBS; rytvela; mice
dc.subject.meshUterus
dc.subject.meshMice, Inbred C57BL
dc.subject.meshStreptococcus agalactiae
dc.subject.meshStreptococcal Infections
dc.subject.meshPremature Birth
dc.subject.meshCyclooxygenase 2
dc.titleInhibition of interleukin-1 signaling protects against Group B Streptococcus-induced preterm birth and fetal loss in mice
dc.typeJournal article
pubs.publication-statusPublished

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