SUPPRESSION OF IMMUNE RESPONSIVENESS - SEX-DIFFERENCES IN PRENATAL ETHANOL EFFECTS

Exposure to ethanol in utero results in changes in the offspring's developing immune system, including thymus lymphocyte subpopulation shifts and functional lymphocyte changes that persist in adult animals. The present study was designed to define further the extent of changes in the immune system that result from fetal ethanol exposure and to compare effects in male and female offspring. In adulthood, male and female offspring from Sprague-Dawley dams fed an ethanol-containing liquid diet (alcohol, A), an isocaloric liquid control diet (pair-fed, PF), or laboratory chow and water (control, C) during pregnancy were tested for several measures of immune competency. Prenatal ethanol exposure differentially affected male and female offspring. Fetal ethanol-exposed males exhibited a decrease in thymocyte number as well as a decreased splenic lymphocyte proliferative response to the T-cell mitogen, concanavalin A (Con A), with a concomitant decrease in recoverable blast cells, when compared with PF and C males. Further, the defect in T-cell proliferation of A males was not due to an inability to produce the critical growth factor, interleukin-2 (IL-2), but to an inability of lymphoblasts to utilize exogenous IL-2. Fetal ethanol-exposed females showed some suggestion of lower thymocyte counts and decreased splenic T-cell proliferative responses to Con A compared to PF and C females. For most of the immune measures, however, no significant differences occurred among A, PF, and C females. In utero ethanol exposure did not significantly alter spleen cell counts or IL-2 production, splenic B-cell proliferation to bacterial lipopolysaccharide (LPS), or thymocyte response to IL-2 in animals of either sex. As expected, however, all females had lower lymphoid organ cell counts and generally better lymphocyte responses than males from the corresponding groups. These data demonstrate that exposure to ethanol during fetal development results in a number of deficits in immune competency that persist in the adult animal. Of particular importance are the observations that these deficits were observed in T-cell-dependent aspects of immunity and were found primarily in male offspring.