4: Prophylactic maternal N-acetylcysteine (NAC) suppresses fetal, though not maternal, IL-6 inflammatory response to lipopolysaccharide (LPS)

Article Outline

• Objective
• Study design
• Results
• Conclusion
• Copyright

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Objective 

Maternal and fetal infections and inflammation have been implicated in the genesis of cerebral palsy and chronic lung disease. High newborn blood proinflammatory cytokines are a marker of fetal inflammatory response syndrome (FIRS), which is associated with acute and long term morbidity. Studies have suggested that changing the redox balance by enhancing the activity or availability of antioxidants may prevent cytokine-induced tissue damage. We sought to determine whether prophylactic administration of NAC, a known antioxidant, can blunt fetal inflammatory responses to maternal LPS-induced inflammation.

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Study design 

Pregnant Sprague Dawley rats (n=28) at 20 days gestation were studied. Maternal rats received intraperitoneal injections of saline (Sal) or N-acetylcysteine (NAC) (300 mg/kg) at time 0, followed by LPS (500 μg/kg) at time 30 min, (Sal-LPS, NAC-LPS). At 6 h after the first injection, rats were sacrificed and IL-6 levels in the fetal and maternal serum were determined by ELISA. Independent effects of NAC (Sal-NAC) and saline (Sal-Sal) were also determined.

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Results 

In response to maternal LPS, maternal and fetal serum IL-6 markedly increased compared to control (maternal 46±3 to 4358±973 pg/ml; fetal 41±4 to 2560±866 pg/ml). NAC given prior to maternal LPS did not change maternal (2692±1458 pg/ml) but significantly reduced the fetal (378±92 pg/ml; p<0.05) proinflammatory IL-6 response. NAC alone (Sal-NAC) did not alter basal maternal or fetal IL-6 levels.

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Conclusion 

Maternal NAC inhibits fetal, though not maternal, IL-6 responses to maternal LPS. These results suggest that NAC administered prophylactically to pregnancies with maternal infection may protect the fetus from adverse inflammatory sequelae, while permitting an appropriate maternal inflammatory response.