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1 Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center and Research and Education Institute, Torrance, CA, USA
* To whom correspondence should be addressed. E-mail: dgayle{at}ucla.edu.
Perinatal infections are a risk factor for fetal neurologic pathologies including cerebral palsy and schizophrenia. Cytokines which are produced as part of the inflammatory response are proposed to partially mediate the neurologic injury. This study investigated the effects of intraperitoneal (i.p.) injections of lipopolysaccharide (LPS) to pregnant rats on the production of cytokines and stress markers in the fetal environment. Gestation day 18 pregnant rats were treated i.p. with LPS (100 µg/kg b.w.) and maternal serum, amniotic fluid, placenta, chorioamnion, and fetal brain were harvested at 1, 6, 12 and 24 h post-treatment to assay for LPS-induced changes in cytokine protein (ELISA) and mRNA (real-time RT-PCR) levels. We observed induction of pro-inflammatory cytokines interleukin-1
(IL-1
), IL-6 and tumor necrosis factor-
(TNF-
) as well as the anti-inflammatory cytokine IL-10 in the maternal serum within 6 h of LPS exposure. Similarly, pro-inflammatory cytokines were induced in the amniotic fluid in response to LPS; however no significant induction of IL-10 was observed in the amniotic fluid. LPS-induced mRNA changes included up-regulation of the stress-related peptide corticotrophin releasing factor (CRF) in the fetal whole brain, TNF-
, IL-6 and IL-10 in the chorioamnion, and TNF-
, IL-1
, and IL-6 in the placenta. These findings suggest that maternal infections may lead to an unbalanced inflammatory reaction in the fetal environment that activates the fetal stress axis.
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