PMID- 15295096
OWN - NLM
STAT- MEDLINE
DCOM- 20050216
LR  - 20081121
IS  - 0031-3998 (Print)
IS  - 0031-3998 (Linking)
VI  - 56
IP  - 4
DP  - 2004 Oct
TI  - Determining the fetal inflammatory response in an experimental model of 
      intrauterine inflammation in rats.
PG  - 541-6
AB  - Intrauterine infection is a risk factor for developmental brain injuries in 
      childhood. A variety of cytokines known to be toxic to developing brain cells 
      have been isolated from mothers or children at risk for developmental 
      disabilities, and these cytokines have been proposed as mediators of these 
      injuries. We have developed a model of intrauterine inflammation that damages the 
      developing white matter and we now hypothesize that selected cytokines are 
      increased after our experimental inflammatory stimulus. Timed-pregnant Fischer 
      344 and Lewis rats were injected with 0.1 mg/kg of lipopolysaccharide (LPS) into 
      the cervix at E15. Tumor necrosis factor-alpha (TNF-alpha), interferon-gamma 
      (IFN-gamma), IL-6, and IL-10 were measured in homogenates of fetal brain and 
      placenta at serial time periods within the first 24 h after the inflammatory 
      stimulus. TNF-alpha was increased 20-fold in the placenta and more than 5-fold in 
      the fetal brain after the stimulus. IFN-gamma was only increased within the fetal 
      brain (20-fold) and IL-6 was only increased in the placenta (10-fold). IL-10 was 
      mildly increased in the placenta and was decreased slightly in the fetal brain. 
      Our observations show that an intrauterine inflammatory stimulus can cause large 
      increases in Th1 cytokines within the fetal brain. The placenta can produce 
      selected cytokines but fails to produce IFN-gamma, suggesting that the fetal 
      immune system produces this cytokine in response to our stimulus. By studying 
      placental and brain cytokine responses in models such as ours, the mechanisms 
      responsible for the damage to developing white matter can be determined.
FAU - Bell, Michael J
AU  - Bell MJ
AD  - Center for Neuroscience Research, Children's Research Institute, Children's 
      National Medical Center, Washington University School of Medicine, Washington, 
      D.C., 20010. USA mbell@cnmc.org
FAU - Hallenbeck, John M
AU  - Hallenbeck JM
FAU - Gallo, Vittorio
AU  - Gallo V
LA  - eng
GR  - K08 HD044716/HD/NICHD NIH HHS/United States
GR  - K12 HD01399/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040804
PL  - United States
TA  - Pediatr Res
JT  - Pediatric research
JID - 0100714
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Brain/immunology/metabolism
MH  - Chorioamnionitis/chemically induced/*immunology
MH  - Disease Models, Animal
MH  - Female
MH  - Fetus/*immunology
MH  - Immune System/*embryology/immunology
MH  - Interferon-gamma/metabolism
MH  - Interleukin-10/metabolism
MH  - Interleukin-6/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Placenta/immunology/metabolism
MH  - Pregnancy
MH  - Rats
MH  - Rats, Inbred F344
MH  - Rats, Inbred Lew
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2004/08/06 05:00
MHDA- 2005/02/17 09:00
CRDT- 2004/08/06 05:00
PHST- 2004/08/06 05:00 [pubmed]
PHST- 2005/02/17 09:00 [medline]
PHST- 2004/08/06 05:00 [entrez]
AID - 01.PDR.0000139407.89883.6B [pii]
AID - 10.1203/01.PDR.0000139407.89883.6B [doi]
PST - ppublish
SO  - Pediatr Res. 2004 Oct;56(4):541-6. doi: 10.1203/01.PDR.0000139407.89883.6B. Epub 
      2004 Aug 4.