Prophylactic maternal n-acetylcysteine before lipopolysaccharide suppresses fetal inflammatory cytokine responses.

Abstract

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). 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. 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. Maternal NAC suppressed fetal and maternal inflammatory responses to maternal LPS. These results suggest that prophylactic NAC may protect the fetus from maternal inflammation.