Camron Chehroudi1, Hugh Kim1, Tricia E Wright2, Abby C Collier3. 1. Centre for Blood Research, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada; Faculty of Dentistry, 2199 Wesbrook Mall, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada. 2. Departments of Obstetrics, Gynecology and Women's Health, and Psychiatry, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, 96813, USA. 3. Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, V6T1Z3, Canada. Electronic address: abby.collier@ubc.ca.
Abstract
INTRODUCTION: Cytokines and vascular endothelial growth factors (VEGF) are involved in all aspects of pregnancy: from placentation, through fetal development, parturition and neonatal well-being. Umbilical cord inflammatory cytokines and/or VEGF have not been well studied with respect to dysregulation associated with disorders of pregnancy or maternal/neonatal outcomes. METHODS: Here we have used multiplex ELISA to screen umbilical cord lysates (comprising cord blood, endothelia and Wharton's jelly, n = 380), for levels of IFN-γ, IL1-β, IL-6, IL-8, IL-10, TNF-α and VEGFs A, C and D and associations with 46 ICD9/10 codes encompassing obstetric, maternal and neonatal variables. RESULTS: No significant differences were observed for IFNγ, VEGFC or VEGFD with any clinical outcomes. The cytokines IL1-β, IL-6, IL-8, IL-10, and TNF-α showed varying levels of induction and suppression with primarily fetal-placental and neonatal complications. The largest number of significant differences between umbilical cytokines and clinical outcomes were observed for chorioamnionitis (IL1-β, IL-6, IL-8, TNF-α), and meconium passage during birth (IL1-β, IL-6, IL-8) where significant pro-inflammatory responses occurred and sex differences in IL-8 expression were noted. In contrast, gonococcal infection showed suppressed immune response significantly lowering IL1-β, IL-6, IL-8, IL-10 and TNF-α. For 12/46 negative pregnancy outcomes, strong suppression of VEGFA occurred. DISCUSSION: Angiogenic and inflammatory changes in the umbilical cord could be detrimental by increasing vascular permeability in the umbilical artery or vein and/or altering vascular tone, either of which would alter blood flow affecting delivery and removal of compounds. Further elucidation of inflammatory responses in the umbilical cord may provide mechanistic understanding of adverse pregnancy outcomes.
INTRODUCTION: Cytokines and vascular endothelial growth factors (VEGF) are involved in all aspects of pregnancy: from placentation, through fetal development, parturition and neonatal well-being. Umbilical cord inflammatory cytokines and/or VEGF have not been well studied with respect to dysregulation associated with disorders of pregnancy or maternal/neonatal outcomes. METHODS: Here we have used multiplex ELISA to screen umbilical cord lysates (comprising cord blood, endothelia and Wharton's jelly, n = 380), for levels of IFN-γ, IL1-β, IL-6, IL-8, IL-10, TNF-α and VEGFs A, C and D and associations with 46 ICD9/10 codes encompassing obstetric, maternal and neonatal variables. RESULTS: No significant differences were observed for IFNγ, VEGFC or VEGFD with any clinical outcomes. The cytokines IL1-β, IL-6, IL-8, IL-10, and TNF-α showed varying levels of induction and suppression with primarily fetal-placental and neonatal complications. The largest number of significant differences between umbilical cytokines and clinical outcomes were observed for chorioamnionitis (IL1-β, IL-6, IL-8, TNF-α), and meconium passage during birth (IL1-β, IL-6, IL-8) where significant pro-inflammatory responses occurred and sex differences in IL-8 expression were noted. In contrast, gonococcal infection showed suppressed immune response significantly lowering IL1-β, IL-6, IL-8, IL-10 and TNF-α. For 12/46 negative pregnancy outcomes, strong suppression of VEGFA occurred. DISCUSSION: Angiogenic and inflammatory changes in the umbilical cord could be detrimental by increasing vascular permeability in the umbilical artery or vein and/or altering vascular tone, either of which would alter blood flow affecting delivery and removal of compounds. Further elucidation of inflammatory responses in the umbilical cord may provide mechanistic understanding of adverse pregnancy outcomes.
Authors: Lisa M Bebell; Kalynn Parks; Mylinh H Le; Joseph Ngonzi; Julian Adong; Adeline A Boatin; Ingrid V Bassett; Mark J Siedner; Alison D Gernand; Drucilla J Roberts Journal: J Infect Dis Date: 2021-12-08 Impact factor: 5.226
Authors: Karla Rio-Aige; Ignasi Azagra-Boronat; Malén Massot-Cladera; Marta Selma-Royo; Anna Parra-Llorca; Sonia González; Izaskun García-Mantrana; Margarida Castell; María J Rodríguez-Lagunas; María Carmen Collado; Francisco José Pérez Cano Journal: Int J Mol Sci Date: 2021-02-10 Impact factor: 5.923