Preterm birth is a leading cause of perinatal morbidity and mortality that is often associated with ascending
infections from the lower genital tract. Recent studies with animal models have suggested that developmental exposure to the environmental toxin
2,3,7,8-tetrachlorodibenzo-p-dioxin (
TCDD) can increase the risk of
preterm birth in the offspring. How
TCDD may modify placental immunity to ascending
infections is unclear. Therefore, we studied the effects of
TCDD treatment on basal and Escherichia coli-stimulated
cytokine production by placental explants. Cultures of second-trimester placentas were treated with up to 40 nM
TCDD for 72 h and then stimulated with 10(7)CFU/ml E. coli for an additional 24h. Concentrations of
cytokines and
PGE2 were measured in
conditioned medium by immunoassay.
TCDD exposure increased
mRNA levels of IL-1β by unstimulated cultures, but no effects on
protein levels of this
cytokine were detected. TNF-α production was unaffected by
TCDD for unstimulated cultures, but pre-treatment with 40 nM
TCDD significantly increased E. coli-stimulated TNF-α production. Both basal and bacteria-stimulated
PGE2 and COX-2 gene expression were enhanced by
TCDD pretreatment. In contrast, production of the anti-inflammatory
cytokine,
IL-10, was reduced by
TCDD pretreatment for both unstimulated and E. coli-stimulated cultures. No effect of
TCDD on the viability of the cultures was detected. These results suggest that
TCDD exposure may shift immunity to enhance a proinflammatory phenotype at the maternal-fetal interface that could increase the risk of
infection-mediated
preterm birth.