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Only recently have researchers begun to study the effect of alcohol on the developing immune system of the fetus. The early evidence is that alcohol can have lasting effects. The [...]

Prenatal ethanol exposure and stress have each been shown to have significant effects on the immune system. This study examined the possible interactive effects of prenatal ethanol exposure and exposure to stress later in life on the immune system. Differential vulnerability to these challenges in female and male offspring was assessed. At 5 to 6 months of age, female and male offspring from prenatal ethanol-exposed (E), pair-fed (PF), and ad libitum-fed control (C) conditions were exposed to 0, 1, or 3 days of cold (4°C). At the end of the cold period, the proliferative response of splenic lymphocytes to the mitogens concanavalin A (Con A) and pokeweed mitogen (PWM) was assessed. The data demonstrate a significant interactive effect between prenatal ethanol exposure and cold stress in female offspring. After 1 day of cold stress, E females had significantly increased PWM-induced lymphocyte proliferation compared with PF and C females, and significantly increased Con A-induced lymphocyte proliferation compared with PF females. There were no differences in PWM or Con A-induced lymphocyte proliferation among E, PF, and C females after 0 or 3 days of cold stress, nor among E, PF, and C males on any test day. Regardless of prenatal treatment, females exposed to 1 or 3 days of cold had significantly greater basal plasma corticosterone levels than females not exposed to cold. In contrast, only E males exposed to 1 or 3 days of cold had significantly increased basal plasma corticosterone levels, compared with E males not exposed to cold; PF and C males showed no significant change in basal corticosterone after cold stress. These data demonstrate that, in response to the challenge of cold stress, changes in lymphocyte proliferation to PWM and Con A may occur selectively in E females. Moreover, the interactive effects of prenatal ethanol and cold stress may result in enhanced rather than suppressed immune responsiveness. [ABSTRACT FROM AUTHOR]

This study evaluated the effects of surrogate fostering as a procedure to control for postnatal effects of ethanol on the maternal female that may indirectly affect the offspring. Effects of fostering on the development of splenic lymphocytes, as well as possible differential effects of fostering on female and male offspring were examined. Litters from prenatal ethanol exposed (E), pair-fed (PF), and ad libitum-fed control (C) condRions were fostered at birth to surrogate untreated dams who had given birth within the same 12-hr period, or were reared by their biological mothers. At 15 and 60 days of age, offspring from each of the conditions were sacrificed and splenic leukocytes were enumerated and analyzed for expression of differentiation antigens, using flow cytometry. At 15 days of age, fostering reduced the percentages of CD45RA+ and CD5+ cells in E compared with PF and in PF compared with C offspring, and reduced the percentage of CD4+ cells in E compared with C offspring. Fostering also had differential effects on E and C offspring, resulting in reduced percentages of CD45RA+ and CD5+ cells in fostered E compared with nonfostered E offspring, but increased percentages of CD45RA+, CD5+, and CD8+ cells in fostered C compared with non-fostered C offspring. Fostering also down-regulated CD5 antigen expression in E compared with C offspring and up-regulated CD4 antigen expression in C offspring compared with their nonfostered counterparts. At 60 days of age, E females overall had higher percentages of CD45RA+ cells compared with C females and higher percentages of CD4+ cells compared with PF and C females. Nonfostered E females had higher percentages of CD5+ cells than nonfostered C females. In contrast, E males overall had greater percentages of CD4+ cells compared with PF and C males. Among males, the percentage of CD5+ cells was increased in nonfostered E compared with nonfostered C, whereas the percentages of CD45RA+ and CD5+ cells were decreased in fostered E males compared with nonfostered E. For both females and males in the nonfostered condition there were no effects of prenatal ethanol treatment on differentiation antigen expression. However, after fostering, E females had higher CD45RA and CD5 antigen expression compared with PF and C females, whereas E males had increased CD4 antigen expression and C males had decreased CD5 antigen expression compared with their nonfostwed Counterparts. These data demonstrate that fostering at birth has differential effects on splenic lymphocyte populations in E, PF, and C offspring. Moreover, the effect of fostering varies with age and has differential long-term effects on female and male offspring. Thus, rather than serving as a control for indirect maternal effects of ethanol on offspring, fostering appears to be a treatment in itself and may actually confound the effects of prenatal ethanol exposure by differentially affecting E, PF, and C females and males. [ABSTRACT FROM AUTHOR]

The present study was undertaken to assess the possible interactive effects of prenatal ethanol exposure and stress in adulthood on lymphocyte populations in rat offspring, and to examine differential vulnerability of males and females to these challenges. Male and female offspring from prenatal ethanol-exposed (E), pair-fed, and ad libitum-fed control conditions were exposed to a 3-week chronic intermittent stress regimen in adulthood. Animals were exposed to two of six different stressors daily, one each at random times in the morning and afternoon, with the same pair of stressors being repeated every 4 days. Following the 3-week stress period, lymphocytes from four compartments (peripheral blood, spleen, thymus, and cervical lymph nodes) were analyzed for expression of differentiation antigens. Data demonstrate that, whereas a number of the effects of prenatal ethanol on lymphocyte populations appeared to be nutritionally mediated, the additional challenge of exposure to stressors differentially affected animals exposed to ethanol prenatally and appeared to have effects primarily in male offspring. Stressed E males had a greater reduction in the number of pan T-cells in the thymus and peripheral blood, compared with nonstressed E males, but showed an increased peripheral blood pan T-antigen expression. Stressed E males also had reduced numbers of peripheral blood CD4+ T-cells and thymic CD4+CD8+ T-cells, compared with controls. In addition, several effects of stress were observed in animals in all three prenatal treatment groups, including decreased numbers of lymph node pan T- and CD4+ T-cells and decreased numbers of total peripheral blood lymphocytes in males, increased numbers of total splenic and thymic lymphocytes in females, and increased numbers of splenic CD8+ T-cells, as well as a decreased ratio of CD4+:CD8+ T-cells in the lymph node and spleen in both males and females. These findings indicate that, although exposure to chronic intermittent stress in adulthood may have marked effects on lymphocyte populations across all treatment groups, specific deficits in the immune system of fetal E animals may become apparent only when these animals are subjected to the additional challenge of stress. Moreover, male and female offspring may be differentially affected by the two challenges of ethanol and stress. [ABSTRACT FROM AUTHOR]

Ethanol is a recognized immunosuppressive agent in the chronic alcoholic. However, the effects of ethanol exposure on the developing immune system have not been extensively investigated. This study evaluated the effects of early postnatal ethanol exposure, via breast milk, on splenic lymphocyte differentiation antigen expression in offspring reared by ethanol-fed mice. Maternal mice were fed a liquid diet containing 20% ethanol-derived calories during pregnancy (E-P), pregnancy and lactation (E-PL), or lactation (E-L). Ad libitumfed (C) and pair-fed (PF) control groups, fed a control liquid diet, were included. Expression of differentiation antigens on splenic lymphocytes from 21-day-old offspring reared by females in 1 of the 3 ethanol exposure conditions was evaluated by flow cytometry. Offspring reared by E-P females had similar numbers of splenic lymphocytes as offspring reared by C and pair-fed during pregnancy (PF-P) females. In contrast, offspring reared by E-PL and E-L females had fewer splenic lymphocytes than both PF-PL and PF-L (respectively), and C offspring. The number of Thy 1.2+, CD4+, CD8+, and IgG+ (B-cell) splenic lymphocytes was reduced in E-PL and E-L offspring compared with PF and C offspring. E-P offspring had fewer CD4+ and IgG+ splenic lymphocytes than C, but not PF-P, offspring. The percentage of Thy 1.2+ splenic lymphocytes was significantly reduced among E-PL and E-L offspring compared with PF-PL and PF-L (respectively), and C offspring. These results suggest that ethanol exposure of female mice during pregnancy, pregnancy and lactation, or lactation alone, alters the phenotypic development of splenic lymphocytes of offspring reared by these females. The greatest effect on differentiation antigen expression occurred when females consumed ethanol during the period of lactation. We speculate that direct exposure of the nursing offspring to ethanol via the breast milk was responsible for the reductions in specific splenic lymphocyte populations. These data demonstrate that mice reared by females fed ethanol during the early postnatal period have a marked depletion of each of the major subpopulations of splenic lymphocytes, and that Thy 1.2+ lymphocytes are differentially sensitive to ethanol. [ABSTRACT FROM AUTHOR]