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

被引:176
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
[21]   Maternal infection and cerebral palsy in infants of normal birth weight [J].
Grether, JK ;
Nelson, KB .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1997, 278 (03) :207-211
[22]  
Halliday HL, 2009, COCHRANE DB SYST REV, DOI [10.1002/14651858.CD001145.pub2, 10.1002/14651858.CD001146.pub2]
[23]   Failure of E. coli bacteria to induce preterm delivery in the rat [J].
Hirsch, Emmet ;
Filipovich, Yana ;
Romero, Roberto .
JOURNAL OF NEGATIVE RESULTS IN BIOMEDICINE, 2009, 8
[24]   Cytokine immunoreactivity in cortical and subcortical neurons in periventricular leukomalacia:: are cytokines implicated in neuronal dysfunction in cerebral palsy? [J].
Kadhim, H ;
Tabarki, B ;
De Prez, C ;
Sébire, G .
ACTA NEUROPATHOLOGICA, 2003, 105 (03) :209-216
[25]   Inflammatory cytokines in the pathogenesis of periventricular leukomalacia [J].
Kadhim, H ;
Tabarki, B ;
Verellen, G ;
De Prez, C ;
Rona, AM ;
Sébire, G .
NEUROLOGY, 2001, 56 (10) :1278-1284
[26]   Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial [J].
Kenyon, S. ;
Pike, K. ;
Jones, D. R. ;
Brocklehurst, P. ;
Marlow, N. ;
Salt, A. ;
Taylor, D. J. .
LANCET, 2008, 372 (9646) :1319-1327
[27]   Childhood outcomes after prescription of antibiotics to pregnant women with preterm rupture of the membranes: 7-year follow-up of the ORACLE I trial [J].
Kenyon, S. ;
Pike, K. ;
Jones, D. R. ;
Brocklehurst, P. ;
Marlow, N. ;
Salt, A. ;
Taylor, D. J. .
LANCET, 2008, 372 (9646) :1310-1318
[28]   Lipopolysaccharide (LPS)-induced intra-uterine fetal death (IUFD) in mice is principally due to maternal cause but not fetal sensitivity to LPS [J].
Kohmura, Y ;
Kirikae, T ;
Kirikae, F ;
Nakano, M ;
Sato, I .
MICROBIOLOGY AND IMMUNOLOGY, 2000, 44 (11) :897-904
[29]   Neuronal injuries induced by perinatal hypoxic-ischemic insults are potentiated by prenatal exposure to lipopolysaccharide:: Animal model for perinatally acquired encephalopathy [J].
Larouche, A ;
Roy, M ;
Kadhim, H ;
Tsanaclis, AM ;
Fortin, D ;
Sébire, G .
DEVELOPMENTAL NEUROSCIENCE, 2005, 27 (2-4) :134-142
[30]   Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study):: a longitudinal cohort study [J].
Larroque, Beatrice ;
Ancel, Pierre-Yves ;
Marret, Stephane ;
Marchand, Laetitia ;
Andre, Monique ;
Arnaud, Catherine ;
Pierrat, Veronique ;
Roze, Jean-Christophe ;
Messer, Jean ;
Thiriez, Gerard ;
Burguet, Antoine ;
Picaud, Jean-Charles ;
Breart, Gerard ;
Kaminski, Monique .
LANCET, 2008, 371 (9615) :813-820