title: The Local and Systemic Immune Response to Intrauterine LPS in the Prepartum Mouse.
abstract: Inflammation plays a key role in human term and preterm labor (PTL). Intrauterine LPS has been widely used to model inflammation-induced complications of pregnancy, including PTL. It has been shown to induce an intense myometrial inflammatory cell infiltration, but the role of LPS-induced inflammatory cell activation in labor onset and fetal demise is unclear. We investigated this using a mouse model of PTL, where an intrauterine injection of 10 μg of LPS (serotype 0111:B4) was given at E16 of CD1 mouse pregnancy. This dose induced PTL at an average of 12.7 h postinjection in association with 85% fetal demise. Flow cytometry showed that LPS induced a dramatic systemic inflammatory response provoking a rapid and marked leucocyte infiltration into the maternal lung and liver in association with increased cytokine levels. Although there was acute placental inflammatory gene expression, there was no corresponding increase in fetal brain inflammatory gene expression until after fetal demise. There was marked myometrial activation of NFκB and MAPK/AP-1 systems in association with increased chemokine and cytokine levels, both of which peaked with the onset of parturition. Myometrial macrophage and neutrophil numbers were greater in the LPS-injected mice with labor onset only; prior to labor, myometrial neutrophils and monocytes numbers were greater in PBS-injected mice, but this was not associated with an earlier onset of labor. These data suggest that intrauterine LPS induces parturition directly, independent of myometrial inflammatory cell infiltration, and that fetal demise occurs without fetal inflammation. Intrauterine LPS provokes a marked local and systemic inflammatory response but with limited inflammatory cell infiltration into the myometrium or placenta.
authors.affiliation: Imperial College Parturition Research Group, Academic Department of Obstetrics & Gynaecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, London, United Kingdom.
authors.forename: Lydia F
authors.initials: LF
authors.lastname: Edey
authors.affiliation: Section of Anaesthetics, Pain Medicine, and Intensive Care, Faculty of Medicine, Chelsea and Westminster Hospital, London, United Kingdom.
authors.forename: Kieran P
authors.initials: KP
authors.lastname: O'Dea
authors.affiliation: Imperial College Parturition Research Group, Academic Department of Obstetrics & Gynaecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, London, United Kingdom.
authors.forename: Bronwen R
authors.initials: BR
authors.lastname: Herbert
authors.affiliation: The International Peace Maternity & Child Health Hospital of China Welfare Institute (IPMCH), Shanghai, China.
authors.forename: Renyi
authors.initials: R
authors.lastname: Hua
authors.affiliation: Gene Transfer Technology Group, Institute for Women's Health, University College London, London, United Kingdom.|Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Simon N
authors.initials: SN
authors.lastname: Waddington
authors.affiliation: Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus DuCane Road, London, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: MacIntyre
authors.affiliation: Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus DuCane Road, London, United Kingdom.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Bennett
authors.affiliation: Section of Anaesthetics, Pain Medicine, and Intensive Care, Faculty of Medicine, Chelsea and Westminster Hospital, London, United Kingdom.
authors.forename: Masao
authors.initials: M
authors.lastname: Takata
authors.affiliation: Imperial College Parturition Research Group, Academic Department of Obstetrics & Gynaecology, Imperial College School of Medicine, Chelsea and Westminster Hospital, London, United Kingdom mark.johnson@imperial.ac.uk.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Johnson
mesh_terms: D000818:Animals; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009215:Myometrium / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology; D014599:Uterus / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B
keywords: chemokines; inflammation; leucocytes; lungs; myometrium