Prophylactic maternal n-acetylcysteine before lipopolysaccharide suppresses fetal inflammatory cytokine responses.
OBJECTIVE
Maternal infection or inflammation may induce fetal inflammatory responses and potentially fetal brain injury. We sought to determine whether prophylactic n-acetylcysteine (NAC), a known antiinflammatory, may modulate the fetal cytokine response to maternal lipopolysaccharide (LPS).


METHODS
Pregnant Sprague Dawley rats (20/21 days = 0.95 gestation; n = 35) received intraperitoneal NAC (300 mg/kg) or saline at time 0 and LPS (500 microg/kg) or saline at 30 minutes. An additional group received NAC following saline. At 6 hours, rats were killed and interleukin (IL)-6, IL-1 beta, and IL-10 levels were determined in fetal and maternal blood.


RESULTS
Following maternal LPS, fetal blood IL-6 (median [25th, 75th] 50 [27, 50] to 2072 [448, 4853] pg/mL) and IL-1 beta (74 [10, 139] to 391 [284, 797] pg/mL) significantly increased. NAC before LPS significantly reduced the fetal IL-6 and IL-1 beta response. Fetal IL-10 was not attenuated by any treatment. NAC attenuated both maternal pro- and antiinflammatory responses to LPS.


CONCLUSIONS
Maternal NAC suppressed fetal and maternal inflammatory responses to maternal LPS. These results suggest that prophylactic NAC may protect the fetus from maternal inflammation.
Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa, Israel. tomor2304@yahoo.com
Ron
R
Beloosesky
Zeev
Z
Weiner
Nizar
N
Khativ
Nir
N
Maravi
Rachel
R
Mandel
Julie
J
Boles
Michael G
MG
Ross
Joseph
J
Itskovitz-Eldor
D000111:Acetylcysteine / Q000008:administration & dosage*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005315:Fetal Diseases / Q000276:immunology / Q000517:prevention & control*; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016753:Interleukin-10; D000111:Acetylcysteine