Prenatal Intra-Amniotic Endotoxin Induces Fetal Gut and Lung Immune Responses and Postnatal Systemic Inflammation in Preterm Pigs

被引:37
作者
Duc Ninh Nguyen [1 ]
Thymann, Thomas [1 ]
Goericke-Pesch, Sandra K. [2 ]
Ren, Shuqiang [1 ]
Wei, Wei [1 ]
Skovgaard, Kerstin [3 ]
Damborg, Peter [4 ]
Brunse, Anders [1 ]
van Gorp, Charlotte [5 ]
Kramer, Boris W. [5 ]
Wolfs, Tim G. [5 ]
Sangild, Per T. [1 ,6 ,7 ]
机构
[1] Univ Copenhagen, Sect Comparat Pediat & Nutr, Dept Vet & Anim Sci, Dyrlaegevej 68, DK-1870 Frederiksberg C, Denmark
[2] Univ Copenhagen, Dept Vet Clin Sci, Sect Vet Reprod & Obstet, Frederiksberg, Denmark
[3] Univ Copenhagen, Dept Vet Dis Biol, Frederiksberg, Denmark
[4] Tech Univ Denmark, Dept Biotechnol & Biomed, Lyngby, Denmark
[5] Maastricht Univ, Sch Oncol & Dev Biol, Dept Pediat, Maastricht, Netherlands
[6] Rigshosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark
[7] Odense Univ Hosp, Dept Pediat, Odense, Denmark
关键词
PREVENT NECROTIZING ENTEROCOLITIS; RISK-FACTOR; HUMAN-MILK; CHORIOAMNIONITIS; INFECTION; MODEL; MATURATION; INFANTS; INJURY; BIRTH;
D O I
10.1016/j.ajpath.2018.07.020
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Prenatal inflammation is a major risk for preterm birth and neonatal morbidity, but its effects on postnatal immunity and organ functions remain unclear. Using preterm pigs as a model for preterm infants, we investigated whether prenatal intra-amniotic (IA) inflammation modulates postnatal systemic immune status and organ functions. Preterm pigs exposed to IA lipopolysaccharide (LPS) for 3 days were compared with controls at birth and postnatal day 5 after formula feeding. IA LPS induced mild chorioamnionitis but extensive intra-amniotic inflammation. There were minor systemic effects at birth (increased blood neutrophil counts), but a few days later, prenatal LPS induced delayed neonatal arousal, systemic inflammation (increased blood leukocytes, plasma cytokines, and splenic bacterial counts), altered serum biochemistry (lower albumin and cholesterol and higher iron and glucose values), and increased urinary protein and sodium excretion. In the gut and lungs, IA LPS-induced inflammatory responses were observed mainly at birth (increased LPS, CXCL8, and IL-1 beta levels and myeloperoxidase-positive cell density, multiple increases in innate immune gene expressions, and reduced villus heights), but not on postnatal day 5 (except elevated lung CXCL8 and diarrhea symptoms). Finally, IA LPS did not affect postnatal gut brush-border enzymes, hexose absorption, permeability, or sensitivity to necrotizing enterocolitis on day 5. Short-term IA LPS exposure predisposes preterm pigs to postnatal systemic inflammation after acute fetal gut and lung inflammatory responses.
引用
收藏
页码:2629 / 2643
页数:15
相关论文
共 61 条
[1]   Delayed growth, motor function and learning in preterm pigs during early postnatal life [J].
Andersen, Anders D. ;
Sangild, Per T. ;
Munch, Sara L. ;
van der Beek, Eline M. ;
Renes, Ingrid B. ;
van Ginneken, Chris ;
Greisen, Gorm O. ;
Thymann, Thomas .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2016, 310 (06) :R481-R492
[2]   Normalization of real-time quantitative reverse transcription-PCR data: A model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets [J].
Andersen, CL ;
Jensen, JL ;
Orntoft, TF .
CANCER RESEARCH, 2004, 64 (15) :5245-5250
[3]   Immune Status in Very Preterm Neonates [J].
Azizia, Mallika ;
Lloyd, Jillian ;
Allen, Meredith ;
Klein, Nigel ;
Peebles, Donald .
PEDIATRICS, 2012, 129 (04) :E967-E974
[4]   Forensic aspects of gene expression signatures for age determination in bruises as evaluated in an experimental porcine model [J].
Barington, Kristiane ;
Jensen, Henrik Elvang ;
Skovgaard, Kerstin .
FORENSIC SCIENCE MEDICINE AND PATHOLOGY, 2017, 13 (02) :151-160
[5]   Histological chorioamnionitis and respiratory outcome in preterm infants [J].
Been, J. V. ;
Zimmermann, L. J. I. .
ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION, 2009, 94 (03) :F218-F225
[6]   Chorioamnionitis as a Risk Factor for Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis [J].
Been, Jasper V. ;
Lievense, Sanne ;
Zimmermann, Luc J. I. ;
Kramer, Boris W. ;
Wolfs, Tim G. A. M. .
JOURNAL OF PEDIATRICS, 2013, 162 (02) :236-+
[7]   Enteral but not parenteral antibiotics enhance gut function and prevent necrotizing enterocolitis in formula-fed newborn preterm pigs [J].
Birck, Malene M. ;
Duc Ninh Nguyen ;
Cilieborg, Malene S. ;
Kamal, Shamrulazhar S. ;
Nielsen, Dennis S. ;
Damborg, Peter ;
Olsen, John E. ;
Lauridsen, Charlotte ;
Sangild, Per T. ;
Thymann, Thomas .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2016, 310 (05) :G323-G333
[8]   Low serum level of high-density lipoprotein cholesterol is a poor prognostic factor for severe sepsis [J].
Chien, JY ;
Jerng, JS ;
Yu, CJ ;
Yang, PC .
CRITICAL CARE MEDICINE, 2005, 33 (08) :1688-1693
[9]  
de Araujo MCK, 1999, EARLY HUM DEV, V56, P1
[10]   A Critical Review of Models of Perinatal Infection [J].
Dean, Justin M. ;
Shi, Zhongjie ;
Fleiss, Bobbi ;
Gunn, Katherine C. ;
Groenendaal, Floris ;
van Bel, Frank ;
Derrick, Matthew ;
Juul, Sandra E. ;
Tan, Sidhartha ;
Gressens, Pierre ;
Mallard, Carina ;
Bennet, Laura ;
Gunn, Alistair J. .
DEVELOPMENTAL NEUROSCIENCE, 2015, 37 (4-5) :289-304