N-acetyl-cysteine suppresses amniotic fluid and placenta inflammatory cytokine responses to lipopolysaccharide in rats.
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]).


METHODS
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.


CONCLUSIONS
NAC inhibition of inflammatory responses may protect the fetus from potential long-term sequelae.
Beloosesky
Ron
R
Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Los Angeles Biomedical Research Institute, Torrance, CA, USA.
Gayle
Dave A
DA
Amidi
Fataneh
F
Nunez
Sonia E
SE
Babu
Jooby
J
Desai
Mina
M
Ross
Michael G
MG
D000111:Acetylcysteine / Q000494:pharmacology*; D000653:Amniotic Fluid / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors*; D005260:Female; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10; D000111:Acetylcysteine