OBJECTIVE: Maternal infections may induce placental, amniotic and, potentially, fetal inflammatory responses. As cytokine responses may be mediated by oxidative stress, we determined whether the antioxidant N-acetyl-cysteine (NAC), can attenuate maternally induced amniotic and placental cytokine responses to maternal infection (modeled by lipopolysaccharide [LPS]). STUDY DESIGN: Gestation day 18 pregnant rats were (1) treated with LPS (100 microg/kg, body weight; intraperitoneally) alone; (2) pretreated with NAC (300 mg/kg body weight; intraperitoneally) 30 minutes before LPS; (3) posttreated with NAC 120 minutes after LPS; or (4) treated with NAC 30 minutes before and 120 minutes after LPS. Six hours after LPS administration, maternal serum and amniotic fluid interleukin-6 (IL-6) and IL-10 levels, and placental IL-6 messenger RNA levels were determined. RESULTS: LPS increased maternal serum IL-6 (50 +/- 25 to 3444 +/- 584 pg/mL) and IL-10 (40 +/- 20 to 958 +/- 339 pg/mL) and amniotic fluid IL-6 (59 +/- 25 to 891 +/- 128 pg/mL). Pretreatment and/or posttreatment with NAC attenuated IL-6 in the maternal serum and amniotic fluid and IL-10 in the amniotic fluid. LPS also induced placental IL-6 messenger RNA that was inhibited by treatment with NAC before and after LPS. CONCLUSION: NAC inhibition of inflammatory responses may protect the fetus from potential long-term sequelae.
OBJECTIVE:Maternal infections may induce placental, amniotic and, potentially, fetal inflammatory responses. As cytokine responses may be mediated by oxidative stress, we determined whether the antioxidant N-acetyl-cysteine (NAC), can attenuate maternally induced amniotic and placental cytokine responses to maternal infection (modeled by lipopolysaccharide [LPS]). STUDY DESIGN: Gestation day 18 pregnant rats were (1) treated with LPS (100 microg/kg, body weight; intraperitoneally) alone; (2) pretreated with NAC (300 mg/kg body weight; intraperitoneally) 30 minutes before LPS; (3) posttreated with NAC 120 minutes after LPS; or (4) treated with NAC 30 minutes before and 120 minutes after LPS. Six hours after LPS administration, maternal serum and amniotic fluid interleukin-6 (IL-6) and IL-10 levels, and placental IL-6 messenger RNA levels were determined. RESULTS:LPS increased maternal serum IL-6 (50 +/- 25 to 3444 +/- 584 pg/mL) and IL-10 (40 +/- 20 to 958 +/- 339 pg/mL) and amniotic fluid IL-6 (59 +/- 25 to 891 +/- 128 pg/mL). Pretreatment and/or posttreatment with NAC attenuated IL-6 in the maternal serum and amniotic fluid and IL-10 in the amniotic fluid. LPS also induced placental IL-6 messenger RNA that was inhibited by treatment with NAC before and after LPS. CONCLUSION:NAC inhibition of inflammatory responses may protect the fetus from potential long-term sequelae.
Authors: Andreas Schmiedl; Jan Behrens; Katja Zscheppang; Erkhembulgan Purevdorj; Dietlinde von Mayersbach; Andrea Liese; Christiane E L Dammann Journal: Am J Physiol Lung Cell Mol Physiol Date: 2011-07-01 Impact factor: 5.464