Determining the fetal inflammatory response in an experimental model of intrauterine inflammation in rats

Pediatr Res. 2004 Oct;56(4):541-6. doi: 10.1203/01.PDR.0000139407.89883.6B. Epub 2004 Aug 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / immunology
  • Brain / metabolism
  • Chorioamnionitis / chemically induced
  • Chorioamnionitis / immunology*
  • Disease Models, Animal
  • Female
  • Fetus / immunology*
  • Immune System / embryology*
  • Immune System / immunology
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / pharmacology
  • Placenta / immunology
  • Placenta / metabolism
  • Pregnancy
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • Tumor Necrosis Factor-alpha / metabolism


  • Interleukin-6
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma