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


CONCLUSIONS
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.
Arjona
Alvaro
A
Endocrine Program, Biomedical Division of the Center of Alcohol Studies and Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901, USA.
Boyadjieva
Nadka
N
Kuhn
Peter
P
Sarkar
Dipak K
DK
D000818:Animals; D002940:Circadian Rhythm; D003602:Cytotoxicity, Immunologic; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D005333:Fetus / Q000187:drug effects; D053804:Granzymes; D007371:Interferon-gamma / Q000032:analysis*; D007694:Killer Cells, Natural / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000032:analysis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000032:analysis*; D013154:Spleen / Q000737:chemistry / Q000276:immunology*
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D000431:Ethanol; D007371:Interferon-gamma; D053804:Granzymes; C509215:Gzmb protein, rat; D012697:Serine Endopeptidases