In utero ethanol exposure impairs defenses against experimental group B streptococcus in the term Guinea pig lung.
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.
Gauthier
Theresa W
TW
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
Young
Paula A
PA
Gabelaia
Levan
L
Tang
Sonja M
SM
Ping
Xiao-Du
XD
Harris
Frank L
FL
Brown
Lou Ann S
LA
D000818:Animals; D000831:Animals, Newborn; D000931:Antidotes / Q000493:pharmacokinetics / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005260:Female; D005978:Glutathione / Q000493:pharmacokinetics / Q000494:pharmacology; D006168:Guinea Pigs; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology; D018613:Microscopy, Confocal; D010587:Phagocytosis / Q000187:drug effects; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000473:pathology; D011247:Pregnancy; D012129:Respiratory Function Tests; D012436:S-Adenosylmethionine / Q000008:administration & dosage / Q000494:pharmacology; D018805:Sepsis / Q000382:microbiology; D013290:Streptococcal Infections / Q000276:immunology* / Q000473:pathology; D013292:Streptococcus agalactiae
D000931:Antidotes; D002492:Central Nervous System Depressants; D000431:Ethanol; D012436:S-Adenosylmethionine; D005978:Glutathione