Prenatal exposure to maternal infection alters cytokine expression in the placenta, amniotic fluid, and fetal brain

Urakubo, Ari; Jarskog, L.Fredrik; Lieberman, Jeffrey A.; Gilmore, John H.

« Previous Next »Schizophrenia Research
Volume 47, Issue 1 , Pages 27-36, 15 January 2001

Prenatal exposure to maternal infection alters cytokine expression in the placenta, amniotic fluid, and fetal brain☆

Ari Urakubo
- Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160, USA
L.Fredrik Jarskog
- Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160, USA
- UNC Mental Health and Neuroscience Research Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160, USA
Jeffrey A. Lieberman
John H. Gilmore
- Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160, USA
- UNC Mental Health and Neuroscience Research Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160, USA
- Corresponding author. Present address: Department of Psychiatry, CB# 7160, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160, USA. Tel.: +1-919-966-6971; fax: +1-919-966-7659

Received 3 September 1999; accepted 24 January 2000.

Abstract

Prenatal exposure to infection appears to increase the risk of schizophrenia and other neurodevelopmental disorders. We have hypothesized that cytokines, generated in response to maternal infection, play a key mechanistic role in this association. E16 timed pregnancy rats were injected i.p. with Escherichia coli lipopolysaccharide (LPS) to model prenatal exposure to infection. Placenta, amniotic fluid and fetal brains were collected 2 and 8h after LPS exposure. There was a significant treatment effect of low-dose (0.5mg/kg) LPS on placenta cytokine levels, with significant increases of interleukin (IL)-1β (P<0.0001), IL-6 (P<0.0001), and tumor necrosis factor-α (TNF-α) (P=0.0001) over the 2 and 8h time course. In amniotic fluid, there was a significant effect of treatment on IL-6 levels (P=0.0006). Two hours after maternal administration of high-dose (2.5mg/kg) LPS, there were significant elevations of placenta IL-6 (P<0.0001), TNF-α (P<0.0001), a significant increase of TNF-α in amniotic fluid (P=0.008), and a small but significant decrease in TNF-α (P=0.035) in fetal brain. Maternal exposure to infection alters pro-inflammatory cytokine levels in the fetal environment, which may have a significant impact on the developing brain.