N-acetylcysteine attenuates the maternal and fetal proinflammatory response to intrauterine LPS injection in an animal model for preterm birth and brain injury.

OBJECTIVE: Maternal immune activation (MIA) is associated with preterm birth (PTB) and abnormal neurologic outcome. We hypothesized that N-acetylcysteine (NAC) would decrease PTB and neonatal brain injury acting as an anti-inflammatory.
METHODS: Pregnant CD-1 mice received intrauterine LPS or saline on day 15/20. They received NAC or saline and were monitored until delivery. Pups were followed and sacrificed on postnatal days 1/30 and brains were collected. Immunostaining for heavy-chain neurofilament protein (NF-H), myelin basic protein (MBP), and proteolipid protein (PLP) was performed. In another group, animals were sacrificed 6 h after treatment, and fetal brain, placenta, and myometrium were collected. Il-6, Il-1β, Il-10, and tumor necrosis factor (TNF)-α mRNA expression was determined. Nonparametric analysis was used for analysis, and pairwise comparisons were performed when appropriate.
RESULTS: Lipopolysaccharide (LPS) caused PTB (79 vs. 0%, p < 0.005), and this was reduced by NAC [0.45 (95% CI: 0.26-0.83), p < 0.008]. LPS increased IL-6 expression in myometrium and placenta. This was attenuated by NAC in myometrium. IL-1β, IL-6, and TNF-α expression increased in the fetal brain with LPS. LPS produced altered NF-H, MBP, and PLP staining, and these effects were attenuated by NAC.
CONCLUSION: NAC attenuates inflammation in this MIA model and reduces PTB and white matter injury. It is an interesting candidate for study for prevention of PTB and neurologic injury.