The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia

Abstract

Maternal infections with bacterial or viral agents during pregnancy are associated with an increased incidence of schizophrenia in the offspring at adulthood although little is known about the mechanism by which maternal infection might affect fetal neurodevelopment. Exposure of pregnant rodents to the bacterial endotoxin, lipopolysaccharide (LPS), results in behavioral deficits in the adult offspring that are relevant to schizophrenia. It is however unknown whether these effects are due to the direct action of the inflammatory stimulus on the developing fetus, or due to secondary immune mediators (cytokines) activated at maternal/fetal sites. In this study we sought to elucidate the site of action of LPS, following a single intraperitoneal (i.p.) injection, in pregnant rats at gestation day 18. Animals received 5 μCi of iodinated LPS (125I-LPS) and its distribution was assessed in maternal/fetal tissues (1–8 h). In addition, induction of the inflammatory cytokines, TNF-α, IL-1β and IL-6, was measured in maternal/fetal tissues following maternal LPS challenge (0.05 mg/kg, i.p.) (2–8 h). 125I-LPS was detected in maternal tissues and placenta, but not the fetus. This distribution was accompanied by significant increases in TNF-α, IL-1β and IL-6 in maternal plasma and placenta, but not in fetal liver or brain. A significant increase in IL-1β was however detected in fetal plasma, possibly due to transfer from the maternal circulation or placenta. Collectively, these data suggest that effects of maternal LPS exposure on the developing fetal brain are not mediated by the direct action of LPS, but via indirect actions at the level of the maternal circulation or placenta.

DOI: 10.1038/sj.mp.4001748

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@article{Ashdown2006TheRO, title={The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia}, author={Helen Ashdown and Yvan Dumont and Marie Ng and Stephen Poole and Patricia Boksa and Giamal N. Luheshi}, journal={Molecular Psychiatry}, year={2006}, volume={11}, pages={47-55} }