Evidence map›Paper›PMID 40993359›Full record

ArticlePediatric research2026

Sex differences in preterm cytokine and inflammasome responses and modulation by exogenous sex steroids.

Matthew McGovern, Lynne A Kelly, Rebecca Finnegan, John F Murphy, John Kelleher, Ashanty M Melo, Catherine M Greene, Eleanor J Molloy

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Article in Pediatric research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Matthew McGovernDiscipline of Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland.
Lynne A KellyDiscipline of Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland. kellyl37@tcd.ie.
Rebecca FinneganDiscipline of Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland.
John F MurphyDepartment of Neonatology, National Maternity Hospital, Holles Street, Dublin, Ireland.
John KelleherNeonatology, Coombe Hospital, Dublin, Ireland.
Ashanty M MeloTrinity Translational Medicine Institute (TTMI) & Trinity Research in Childhood Centre (TRICC), Trinity College Dublin, Dublin, Ireland.
Catherine M GreeneDepartment of Clinical Microbiology, The Royal College of Surgeons in Ireland, Dublin, Ireland.
Eleanor J MolloyDiscipline of Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPreterm infants are at increased risk of sepsis compared to adults and older children. Preterm immune cells have altered cytokine responses compared to term neonates and adults and all have sex-related differences in immunity. We examined inflammasome activation and cytokines with endotoxin and sex steroid hormones between preterm and term neonates.

methodsPreterm (n = 40) and term (n = 32) peripheral blood samples were incubated with Lipopolysaccharide (LPS), Estradiol (E2), Progesterone (Pg) or Pam3CSK4 and biomarkers were analysed by ELISA. Inflammasome genes, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), Interleukin-1 beta (IL1-β) and Absent In Melanoma 2 (AIM 2) were analysed with Taqman RT-PCR.

resultsIL-1β cytokine expression was reduced by female sex hormones and notably the effect of estradiol was greatest in the preterm population. Female preterm neonates were more responsive to the anti-inflammatory effect of progesterone than male preterm infants. Term neonates had higher IL-1β, IL-18 and IL-1RA expression than preterm infants. Overall, in preterms, E2 and Pg lowered cytokine expression levels. Inflammasome gene expression profiles did not differ between preterm male and female neonates.

conclusionSex hormones altered the expression of multiple cytokines, and cytokine responses differ by sex. Gestation plays an important role in the inflammatory response, and we note term infants have a more robust profile while preterm infants are more responsive to hormonal stimulus. Female sex hormones have an important role in modulating neonatal immune response and may contribute to the female immune advantage. IMPACT: Female sex hormones play an important role in modulating the neonatal immune response. This is reflected clinically by better bacterial clearance and improved sepsis outcome in females. This study aims to test the hypothesis that male and female neonates differ in their cytokine and inflammasome response and in response to endotoxin and sex steroid hormones. In preterm infants there is a sex difference in IL-1b responses which is observed rapidly following endotoxin stimulation. Differing immune responses according to sex has implications for future clinical application. Further work to characterise these sex differences may help in guiding therapy during sepsis.

Indexed as

CytokinesGonadal Steroid HormonesInfant, PrematureInflammasomesEstradiolFemaleHumansInfant, NewbornInterleukin-1betaLipopolysaccharidesMaleNLR Family, Pyrin Domain-Containing 3 ProteinProgesteroneSex CharacteristicsSex FactorsCytokinesEstradiolGonadal Steroid HormonesInflammasomesInterleukin-1betaLipopolysaccharidesNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanProgesterone

Identifiers

PMID40993359
PMCPMC13102689

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.