Immune alterations in geriatric mice dosed subacutely with diethylstilbestrol (DES)

Exposure to both physiological and pharmacological doses of estrogenic compounds has been reported to alter immunologic responses in humans as well as in developmental and adult murine models. Despite the current therapeutic use of potent estrogens, including diethylstilbestrol (DES), in geriatric human disorders, elucidation of the effects of these agents on the aged immune system is limited. The present report describes highly significant alterations in the thymus and bone marrow of aged mice (21 +/- 1 months) exposed subacutely to DES. Severe thymic hypocellularity developed in treated mice following five consecutive days of intraperitoneal injection with 1.5 or 6.0 mg kg(-1) DES. Cell maturation within the thymus was also affected, as indicated by a significant decrease in CD4+8+ cells and a concomitant increase in CD4-8- cells. Cellularity of the bone marow was unchanged by DES. However, significant changes were observed in percentages of bone marrow cells expressing surface antigens CD45 (common leukocyte lineage), Mac-1 (macrophage lineage) and CD45R (B-lineage lymphocytes). Both percentages and total numbers of cells in the spleen expressing Thy 1.2 (T-lineage lymphocytes) were also reduced. These immune changes in geriatric mice exposed to DES were similar in direction but more severe than those reported in either young adult or perinatal models. These data may suggest a need for considering the geriatric immune system separately from other age groups when determining effects of immunosuppressive or immunotoxic compound exposure.