Dehydroepiandrosterone sulfate decreases the interleukin-2-mediated overactivity of the natural killer cell compartment in senile dementia of the Alzheimer type

Since dehydroepiandrosterone su if ate (DH EAS) has been involved in the re gulation of cellular immunity, the aim of the presence study was to evaluat e whether the age-dependent reduction of DHEAS was associated with changes of natural killer (NK) immune function in healthy elderly subjects and in p atients with senile dementia of the Alzheimer type (SDAT). Circulating DHEA S was determined throughout 24 h (circadian profile). NK cytotoxic activity was measured as spontaneous and induced cytotoxicity during exposure with DHEAS (10(-7) M), interleukin-2 (IL-2; 100 IU) and IL-2 (100 lU) coincubate d with DHEAS (10(-7) M). DHEAS was significantly reduced in healthy elderly subjects (mesor M +/- SD = 2.3 +/- 0.5 mu mol/l) and SDAT (1.6 +/- 0.4 mu mol/l) patients compared to healthy young subjects (6.7 +/- 0.9 mu mol/l; p < 0.001); significant differences were also found when healthy elderly sub jects and SDAT patients were compared (p < 0.01). A significant inverse cor relation between age and DHEAS levels was demonstrated in SDAT and healthy elderly subjects (p < 0.05). The decrease in 24-hour DHEAS secretion was as sociated with a higher NK cytotoxic response to DHEAS in the healthy elderl y subject group than in healthy subjects of young age (p < 0.01). Increased NK cell activity during IL-2 incubation was found in patients with SDAT in comparison with the healthy elderly subject (p < 0.001). On the contrary, NK cell cytotoxic response of SDAT patients was less pronounced during DHEA S exposure and when DHEAS was coincubated with IL-2 (p < 0.001). These data suggest an immunomodulatory role of DHEAS on NK functional activity in phy siological aging and SDAT. The antagonizing effect of DHEAS on NK overactiv ity during exposure with cytokines might counteract some neuroimmune compon ents related to the pathogenesis and progression of the disease.