Arjona Alvaro, Boyadjieva Nadka, Kuhn Peter, Sarkar Dipak K
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.
Alcohol Clin Exp Res. 2006 Jun;30(6):1039-44. doi: 10.1111/j.1530-0277.2006.00117.x.
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.
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.
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.
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.
昼夜节律（以及每日节律）是周期为24小时振荡的生理事件。昼夜节律紊乱可能会妨碍针对感染和癌症的免疫反应。几种免疫机制，如自然杀伤（NK）细胞功能，呈现每日节律。尽管已知乙醇对发育中的胎儿的许多系统（包括免疫系统）是一种强效毒素，但胎儿乙醇暴露对昼夜免疫功能的长期影响尚未得到研究。
测定成年雄性大鼠脾脏中细胞毒性因子（颗粒酶B和穿孔素）、干扰素-γ（IFN-γ）和NK细胞细胞毒性活性的每日节律，这些成年雄性大鼠来自孕期喂食普通食物或含乙醇液体饮食或配对喂食等热量液体饮食的母亲。
我们发现，在胎儿期接触乙醇的成年大鼠，其颗粒酶B和IFN-γ的生理节律出现显著改变，且与NK细胞细胞毒性活性降低有关。
这些数据表明，胎儿乙醇暴露会导致特定免疫节律的永久性改变，这可能部分是产前暴露于酒精的儿童出现免疫损害的原因。
