title: Anti-inflammatory prostaglandins for the prevention of preterm labour.
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.
authors.affiliation: Parturition 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.
authors.forename: Lynne
authors.initials: L
authors.lastname: Sykes
authors.affiliation: Parturition 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.
authors.forename: David A
authors.initials: DA
authors.lastname: MacIntyre
authors.affiliation: Parturition 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.
authors.forename: Tiong Ghee
authors.initials: TG
authors.lastname: Teoh
authors.affiliation: Parturition 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.
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Bennett
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007752:Obstetric Labor, Premature / Q000517:prevention & control*; D011247:Pregnancy; D011453:Prostaglandins / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D011453:Prostaglandins