Can statins reduce a systemic inflammatory response during pregnancy in an animal model?

The objective of this study was to determine the effect of statins on inflammatory response in a mouse model of inflammation during gestation. CD1 mice on day 15 of gestation were randomly allocated to intraperitoneal LPS injection (250 μg) or control (saline). Two hours following LPS injection, mice were injected with simvastatin, pravastatin (both 10 mg/g of body weight in saline) or saline, resulting in four study groups: Control (n=9), LPS/Saline (n=9), LPS/Simv (n=10), LPS/Prav (n=9). Animals were sacrificed 6 hours after LPS. Pro-inflammatory cytokine concentrations in maternal plasma, fetal brains, placentas, fetal membranes, and amniotic fluid were determined using xMAP technology. Fetal samples were separated by gender. Maternal serum CRP concentrations were also determined. Results were analyzed using Kruskal-Wallis ANOVA with post-hoc tests as appropriate (statistical significance: p< 0.05). Intraperitoneal injection of LPS successfully induced a statistically significant inflammatory response in both male and female fetal brain, placenta, fetal membranes, amniotic fluid, and maternal plasma, as shown through increased levels of IL-1β, IL-6 and TNF-a. CRP concentration was also significantly higher in maternal serum after LPS injection. Neither simvastatin nor pravastatin had a statistically significant effect on cytokine and CRP levels in any tissues investigated. In a mouse model of maternal inflammation, LPS injection increases inflammatory cytokines in fetal brain, placenta, membranes, amniotic fluid, and maternal plasma, as well as maternal CRP concentrations. Since previous studies have shown an anti-inflammatory effect with statin administration prior to induction of inflammation, we hypothesize that our findings could have resulted from insufficient dosage and/or timing of statin administration. Further study will be needed to elucidate these possibilities.