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Anti-inflammatory prostaglandins for the prevention of preterm labour
Lynne Sykes1, David A MacIntyre2, Tiong Ghee Teoh2
1Parturition Research GroupDepartment of Surgery and Cancer, Institute of Reproduction and Developmental Biology, Imperial College London, London W12 0NN, UKSt Mary's HospitalImperial College Healthcare NHS Trust, London W1 2NY, UK l.sykes@imperial.ac.uk.
Insights
Inflammation contributes to preterm birth, a major cause of newborn complications. Anti-inflammatory strategies, like using specific prostaglandins (PGs), show promise in preventing preterm labor and improving infant survival.
Area of Science:
- Reproductive biology
- Neonatal health
- Inflammation research
Background:
- Preterm birth affects 10-12% of pregnancies, causing significant neonatal mortality and morbidity.
- Current tocolytic therapies for preterm labor lack substantial improvement in neonatal outcomes.
- Infection-induced inflammation is a direct cause of preterm labor and a risk factor for poor neonatal outcomes.
Purpose of the Study:
- To explore anti-inflammatory strategies for preventing preterm labor and improving neonatal outcomes.
- To investigate the role of Nuclear factor kappa B (NFκB) in labor-associated and inflammatory gene expression.
- To evaluate the potential of anti-inflammatory prostaglandins (PGs) as a therapeutic approach.
Main Methods:
- Review of current understanding of inflammation in labor.
- Examination of NFκB as a therapeutic target.
- In vitro studies on 15-deoxy-Δ(12,14)PGJ2 (15d-PGJ2) effects on NFκB in human cells.
- In vivo studies on 15d-PGJ2 in a mouse model of preterm labor.
Main Results:
- NFκB controls genes involved in labor and inflammation.
- 15d-PGJ2, an anti-inflammatory PG, inhibits NFκB in vitro.
- 15d-PGJ2 delays inflammation-induced preterm labor in mice and increases pup survival.
Conclusions:
- Targeting NFκB is a promising therapeutic strategy for preterm labor and reducing neonatal inflammation.
- Anti-inflammatory PGs, such as 15d-PGJ2, may offer a novel approach to prevent preterm birth.
- Further research into anti-inflammatory PGs could lead to improved neonatal outcomes.
Abstract:
Preterm birth occurs in 10-12% of pregnancies and is the primary cause of neonatal mortality and morbidity. Tocolytic therapies have long been the focus for the prevention of preterm labour, yet they do not significantly improve neonatal outcome. A direct causal link exists between infection-induced inflammation and preterm labour. As inflammation and infection are independent risk factors for poor neonatal outcome, recent research focus has been shifted towards exploring the potential for anti-inflammatory strategies. Nuclear factor kappa B (NFκB) is a transcription factor that controls the expression of many labour-associated genes including PTGS2 (COX2), prostaglandins (PGs) and the oxytocin receptor (OXTR) as well as key inflammatory genes. Targeting the inhibition of NFκB is therefore an attractive therapeutic approach for both the prevention of preterm labour and for reducing neonatal exposure to inflammation. While PGs are considered to be pro-labour and pro-inflammatory, the cyclopentenone PG 15-deoxy-Δ(12,14)PGJ2 (15d-PGJ2) exhibits anti-inflammatory properties via the inhibition of NFκB in human amniocytes, myocytes and peripheral blood mononuclear cells in vitro. 15d-PGJ2 also delays inflammation-induced preterm labour in the mouse and significantly increases pup survival. This review examines the current understanding of inflammation in the context of labour and discusses how anti-inflammatory PGs may hold promise for the prevention of preterm labour and improved neonatal outcome.
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