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

Prenatal exposure to infection appears to increase the risk of schizophreni a and other neurodevelopmental disorders. We have hypothesized that cytokin es, generated in response to maternal infection, play a key mechanistic rol e in this association. E16 timed pregnancy rats were injected i.p. with Esc herichia coil lipopolysaccharide (LPS) to model prenatal exposure to infect ion. Placenta. amniotic fluid and fetal brains were collected 2 and 8 h aft er LPS exposure. There was a significant treatment effect of low-dose (0.5 mg/kg) LPS on placenta cytokine levels, with significant increases of inter leukin (IL)-1 beta (P < 0.0001), IL-6 (P < 0.0001). and tumor necrosis fact or-alpha (TNF-alpha) (P = 0.0001) over the 2 and 8 h time course. In amniot ic fluid, there was a significant effect of treatment on IL-6 levels (P = 0 .0006). Two hours after maternal administration of high-dose (2.5 mg/kg) LP S, there were significant elevations of placenta IL-6 (P < 0.0001), TNF-<al pha> (P < 0.0001), a significant increase of TNF-<alpha> in amniotic fluid (P = 0.008), and a small but significant decrease in TNF-alpha (P = 0.035) in fetal brain. Maternal exposure to infection alters pro-inflammatory cyto kine levels in the fetal environment, which may have a significant impact o n the developing brain. (C) 2001 Elsevier Science B.V. All rights reserved.