In utero ethanol exposure impairs defenses against experimental group B streptococcus in the term Guinea pig lung

Alcohol Clin Exp Res. 2009 Feb;33(2):300-6. doi: 10.1111/j.1530-0277.2008.00833.x. Epub 2008 Nov 19.


Background: The effects of fetal alcohol exposure on the risks of neonatal lung injury and infection remain under investigation. The resident alveolar macrophage (AM) is the first line of immune defense against pulmonary infections. In utero ethanol (ETOH) exposure deranges the function of both premature and term guinea pig AM. We hypothesized that fetal ETOH exposure would increase the risk of pulmonary infection in vivo.

Methods: We developed a novel in vivo model of group B Streptococcus (GBS) pneumonia using our established guinea pig model of fetal ETOH exposure. Timed-pregnant guinea pigs were pair fed +/-ETOH and some were supplemented with the glutathione (GSH) precursor S-adenosyl-methionine (SAM-e). Term pups were given GBS intratracheally while some were pretreated with inhaled GSH prior to the experimental GBS. Neonatal lung and whole blood were evaluated for GBS while isolated AM were evaluated using fluorescent microscopy for GBS phagocytosis.

Results: Ethanol-exposed pups demonstrated increased lung infection and sepsis while AM phagocytosis of GBS was deficient compared with control. When SAM-e was added to the maternal diet containing ETOH, neonatal lung and systemic infection from GBS was attenuated and AM phagocytosis was improved. Inhaled GSH therapy prior to GBS similarly protected the ETOH-exposed pup from lung and systemic infection.

Conclusions: In utero ETOH exposure impaired the neonatal lung's defense against experimental GBS, while maintaining GSH availability protected the ETOH-exposed lung. This study suggested that fetal alcohol exposure deranges the neonatal lung's defense against bacterial infection, and support further investigations into the potential therapeutic role for exogenous GSH to augment neonatal AM function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Antidotes / pharmacokinetics
  • Antidotes / pharmacology
  • Body Weight / drug effects
  • Central Nervous System Depressants / antagonists & inhibitors
  • Central Nervous System Depressants / toxicity*
  • Ethanol / antagonists & inhibitors
  • Ethanol / toxicity*
  • Female
  • Glutathione / pharmacokinetics
  • Glutathione / pharmacology
  • Guinea Pigs
  • Lung / pathology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / immunology
  • Microscopy, Confocal
  • Phagocytosis / drug effects
  • Pneumonia, Bacterial / immunology*
  • Pneumonia, Bacterial / pathology
  • Pregnancy
  • Respiratory Function Tests
  • S-Adenosylmethionine / administration & dosage
  • S-Adenosylmethionine / pharmacology
  • Sepsis / microbiology
  • Streptococcal Infections / immunology*
  • Streptococcal Infections / pathology
  • Streptococcus agalactiae*


  • Antidotes
  • Central Nervous System Depressants
  • Ethanol
  • S-Adenosylmethionine
  • Glutathione