482: Maternal lipopolysaccharide (LPS) induced inflammation during pregnancy programs impaired offspring innate immune responses

Abstract

ObjectiveWe have shown previously that maternal LPS induces pro-inflammatory cytokine responses in the placental and fetal blood. Although the preterm fetal innate immune response is responsive, we hypothesized that early activation of fetal inflammatory pathways may impact the ultimate development of immune competency. We sought to determine whether acute maternal exposure to LPS at 18 days of gestation would alter offspring pro- and anti-inflammatory responses.Study DesignPregnant Sprague Dawley rats (n=8) at 18 days′ gestation received intraperitoneal injections of saline or LPS (500 μg/kg). Male and female pups (n=34) were delivered spontaneously (p21) and allowed to mature until postnatal day 24 (p24) when they received i.p injection of LPS (200 μg/kg). At 4 hours after the injection, rats were sacrificed and IL-6, IL-1β and IL-10 levels in the plasma were determined by ELISA.ResultsIn response to LPS, the pups of the control saline injected dams had significantly higher pro-inflammatory IL-6 and IL-1β when compared to the pups of the LPS injected dams (4774±510 vs 2601±727 pg/ml and 1677±102 vs 456±198 pg/ml; p<0.05, respectively). LPS induced a small anti-inflammatory IL-10 response in the pups of saline treated dams which was almost abolished in pups of LPS dams (127±17 vs 65±17 pg/ml, p<0.05). The decreased offspring inflammatory response to LPS was demonstrated both in the males and females.ConclusionPrenatal maternal exposure to LPS alters the pups innate immune response to inflammatory/infectious stimuli. These results suggest that maternal inflammatory exposures during pregnancy (eg, pyelonephritis) may impair newborn innate responses and increase susceptibility to infection. ObjectiveWe have shown previously that maternal LPS induces pro-inflammatory cytokine responses in the placental and fetal blood. Although the preterm fetal innate immune response is responsive, we hypothesized that early activation of fetal inflammatory pathways may impact the ultimate development of immune competency. We sought to determine whether acute maternal exposure to LPS at 18 days of gestation would alter offspring pro- and anti-inflammatory responses. We have shown previously that maternal LPS induces pro-inflammatory cytokine responses in the placental and fetal blood. Although the preterm fetal innate immune response is responsive, we hypothesized that early activation of fetal inflammatory pathways may impact the ultimate development of immune competency. We sought to determine whether acute maternal exposure to LPS at 18 days of gestation would alter offspring pro- and anti-inflammatory responses. Study DesignPregnant Sprague Dawley rats (n=8) at 18 days′ gestation received intraperitoneal injections of saline or LPS (500 μg/kg). Male and female pups (n=34) were delivered spontaneously (p21) and allowed to mature until postnatal day 24 (p24) when they received i.p injection of LPS (200 μg/kg). At 4 hours after the injection, rats were sacrificed and IL-6, IL-1β and IL-10 levels in the plasma were determined by ELISA. Pregnant Sprague Dawley rats (n=8) at 18 days′ gestation received intraperitoneal injections of saline or LPS (500 μg/kg). Male and female pups (n=34) were delivered spontaneously (p21) and allowed to mature until postnatal day 24 (p24) when they received i.p injection of LPS (200 μg/kg). At 4 hours after the injection, rats were sacrificed and IL-6, IL-1β and IL-10 levels in the plasma were determined by ELISA. ResultsIn response to LPS, the pups of the control saline injected dams had significantly higher pro-inflammatory IL-6 and IL-1β when compared to the pups of the LPS injected dams (4774±510 vs 2601±727 pg/ml and 1677±102 vs 456±198 pg/ml; p<0.05, respectively). LPS induced a small anti-inflammatory IL-10 response in the pups of saline treated dams which was almost abolished in pups of LPS dams (127±17 vs 65±17 pg/ml, p<0.05). The decreased offspring inflammatory response to LPS was demonstrated both in the males and females. In response to LPS, the pups of the control saline injected dams had significantly higher pro-inflammatory IL-6 and IL-1β when compared to the pups of the LPS injected dams (4774±510 vs 2601±727 pg/ml and 1677±102 vs 456±198 pg/ml; p<0.05, respectively). LPS induced a small anti-inflammatory IL-10 response in the pups of saline treated dams which was almost abolished in pups of LPS dams (127±17 vs 65±17 pg/ml, p<0.05). The decreased offspring inflammatory response to LPS was demonstrated both in the males and females. ConclusionPrenatal maternal exposure to LPS alters the pups innate immune response to inflammatory/infectious stimuli. These results suggest that maternal inflammatory exposures during pregnancy (eg, pyelonephritis) may impair newborn innate responses and increase susceptibility to infection. Prenatal maternal exposure to LPS alters the pups innate immune response to inflammatory/infectious stimuli. These results suggest that maternal inflammatory exposures during pregnancy (eg, pyelonephritis) may impair newborn innate responses and increase susceptibility to infection.