IL-1 Receptor Antagonist Protects against Placental and Neurodevelopmental Defects Induced by Maternal Inflammation

被引:171
作者
Girard, Sylvie
Tremblay, Luc [2 ,3 ]
Lepage, Martin [2 ,3 ]
Sebire, Guillaume [1 ]
机构
[1] Univ Sherbrooke, CHU Sherbrooke, Dept Pediat, Lab Neurol Pediat,Fac Med & Sci Sante, Sherbrooke, PQ J1H 5N4, Canada
[2] Univ Sherbrooke, Fac Med & Sci Sante, Ctr Imagerie Mol Sherbrooke, Sherbrooke, PQ J1H 5N4, Canada
[3] Univ Sherbrooke, Fac Med & Sci Sante, Dept Med Nucl & Radiobiol, Sherbrooke, PQ J1H 5N4, Canada
关键词
TUMOR-NECROSIS-FACTOR; WHITE-MATTER INJURY; 7-YEAR FOLLOW-UP; CEREBRAL-PALSY; BRAIN-INJURY; PRETERM INFANTS; FETAL-DEATH; PERIVENTRICULAR LEUKOMALACIA; CHILDHOOD OUTCOMES; PREGNANT-WOMEN;
D O I
10.4049/jimmunol.0903349
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The precise role of maternal bacterial infection and inflammation occurring at the end of gestation is a controversial matter. Although it is recognized as an independent risk factor for neurodevelopmental diseases such as cerebral palsy, mental deficiency, and autism, it remains unclear whether it is causal or simply associated with the diseases. In this study, we demonstrate that IL-1 plays a key role in mediating severe placental damage and neurodevelopmental anomalies in offspring. Our results show that end of gestation exposure of pregnant rats to systemic microbial product (LPS) triggers placental inflammation and massive cell death, fetal. mortality, and both forebrain white matter and motor behavioral alterations in the offspring. All these effects are alleviated by the coadministration of IL-1 receptor antagonist with LPS, suggesting a possible protective treatment against human placental and fetal brain damage. The Journal of Immunology, 2010, 184: 3997-4005.
引用
收藏
页码:3997 / 4005
页数:9
相关论文
共 59 条
  • [1] Transfer of proinflammatory cytokines across term placenta
    Aaltonen, R
    Heikkinen, TA
    Hakala, K
    Laine, K
    Alanen, A
    [J]. OBSTETRICS AND GYNECOLOGY, 2005, 106 (04) : 802 - 807
  • [2] The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia
    Ashdown, H
    Dumont, Y
    Ng, M
    Poole, S
    Boksa, P
    Luheshi, GN
    [J]. MOLECULAR PSYCHIATRY, 2006, 11 (01) : 47 - 55
  • [3] Perinatal white matter injury: The changing spectrum of pathology and emerging insights into pathogenetic mechanisms
    Back, Stephen A.
    [J]. MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS, 2006, 12 (02): : 129 - 140
  • [4] Systematic Review and Stratified Meta-analysis of the Efficacy of Interleukin-1 Receptor Antagonist in Animal Models of Stroke
    Banwell, Victoria
    Sena, Emily S.
    Macleod, Malcolm R.
    [J]. JOURNAL OF STROKE & CEREBROVASCULAR DISEASES, 2009, 18 (04) : 269 - 276
  • [5] Antenatal glucocorticoid treatment and cystic periventricular leukomalacia in very premature infants
    Baud, O
    Foix-L'Helias, L
    Kaminski, M
    Audibert, F
    Jarreau, PH
    Papiernik, E
    Huon, C
    Lepercq, J
    Dehan, M
    Lacaze-Masmonteil, T
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1999, 341 (16) : 1190 - 1196
  • [6] Effects of intrauterine inflammation on developing rat brain
    Bell, MJ
    Hallenbeck, JM
    [J]. JOURNAL OF NEUROSCIENCE RESEARCH, 2002, 70 (04) : 570 - 579
  • [7] Magnetic resonance imaging of the normal placenta
    Blaicher, W
    Brugger, PC
    Mittermayer, C
    Schwindt, J
    Deutinger, J
    Bernaschek, G
    Prayer, D
    [J]. EUROPEAN JOURNAL OF RADIOLOGY, 2006, 57 (02) : 256 - 260
  • [8] Targeting IL-1 in inflammatory disease: New opportunities for therapeutic intervention
    Braddock, M
    Quinn, A
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (04) : 1 - 10
  • [9] Brain injury induced by intracerebral injection of interleukin-1beta and tumor necrosis factor-alpha in the neonatal rat
    Cai, ZW
    Lin, SY
    Pang, Y
    Rhodes, PG
    [J]. PEDIATRIC RESEARCH, 2004, 56 (03) : 377 - 384
  • [10] Cytokine induction in fetal rat brains and brain injury in neonatal rats after maternal lipopolysaccharide administration
    Cai, ZW
    Pan, ZL
    Pang, Y
    Evans, OB
    Rhodes, PG
    [J]. PEDIATRIC RESEARCH, 2000, 47 (01) : 64 - 72