ENDOGENOUS GLUCOCORTICOIDS INDUCED BY A CHEMICAL STRESSOR (ETHANOL) CAUSE APOPTOSIS IN THE SPLEEN IN B6C3F1 FEMALE MICE

Stress-induced increases in glucocorticoid levels can cause apoptosis in immature thymocytes, but it is not known if glucocorticoids at thes e levels can also cause apoptosis in peripheral lymphocytes, In the pr esent study, mice were exposed to ethanol (EtOH) in a model designed t o represent binge drinking, This induces a substantial stress response , including an increase in corticosterone levels, Apoptosis in the spl een was evaluated using terminal deoxynucleotidyl transferase dUTP nic k end labeling (TUNEL) with fluorescein-labeled dUTP. Flow cytometric analysis demonstrated a significant increase in the percentage of apop totic cells in the spleen 2-6 h after administration of EtOH (3-6% apo ptotic cells in treated mice vs 0.2-2% in controls), This increase was blocked by the glucocorticoid antagonist, RU 486, and administration of exogenous corticosterone in a manner that produced similar blood le vels and kinetics as noted in EtOH-treated mice produced similar level s of apoptosis. Fluorescein-labeled Annexin V was used to confirm incr eased numbers of apoptotic cells in the spleen in EtOH-treated mice, T hese results indicate that stress-induced glucocorticoids are sufficie nt to induce apoptosis in the spleen, and this may be one mechanism by which stress responses cause immunosuppression. (C) 1998 Academic Pre ss.