Fetal ethanol exposure disrupts the daily rhythms of splenic granzyme B, IFN-gamma, and NK cell cytotoxicity in adulthood

Alcohol Clin Exp Res. 2006 Jun;30(6):1039-44. doi: 10.1111/j.1530-0277.2006.00117.x.

Abstract

Background: Circadian (and daily) rhythms are physiological events that oscillate with a 24-hour period. Circadian disruptions may hamper the immune response against infection and cancer. Several immune mechanisms, such as natural killer (NK) cell function, follow a daily rhythm. Although ethanol is known to be a potent toxin for many systems in the developing fetus, including the immune system, the long-term effects of fetal ethanol exposure on circadian immune function have not been explored.

Methods: Daily rhythms of cytotoxic factors (granzyme B and perforin), interferon-gamma (IFN-gamma), and NK cell cytotoxic activity were determined in the spleens of adult male rats obtained from mothers who were fed during pregnancy with chow food or an ethanol-containing liquid diet or pair-fed an isocaloric liquid diet.

Results: We found that adult rats exposed to ethanol during their fetal life showed a significant alteration in the physiological rhythms of granzyme B and IFN-gamma that was associated with decreased NK cell cytotoxic activity.

Conclusion: These data suggest that fetal ethanol exposure causes a permanent alteration of specific immune rhythms that may in part underlie the immune impairment observed in children prenatally exposed to alcohol.

Publication types

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

MeSH terms

  • Animals
  • Circadian Rhythm
  • Cytotoxicity, Immunologic
  • Ethanol / administration & dosage*
  • Female
  • Fetus / drug effects
  • Granzymes
  • Interferon-gamma / analysis*
  • Killer Cells, Natural / immunology*
  • Membrane Glycoproteins / analysis
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Pregnancy
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Serine Endopeptidases / analysis*
  • Spleen / chemistry
  • Spleen / immunology*

Substances

  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Perforin
  • Ethanol
  • Interferon-gamma
  • Granzymes
  • Gzmb protein, rat
  • Serine Endopeptidases