DECREASED IMMUNOSUPPRESSIVE EFFECT OF CORTISOL ON NATURAL-KILLER CYTOTOXIC ACTIVITY IN SENILE DEMENTIA OF THE ALZHEIMER-TYPE

Former studies have indicated alterations of the cytotoxic activity of natural killer (NK) cells in senile dementia of the Alzheimer type (S DAT). These changes may be related to the increased reactivity of NK c ells with cytokines, even if an impairment of the immunosuppressive ef fect of glucocorticoids cannot be excluded. In the present study we ha ve demonstrated a lower immunosuppressive effect of cortisol on NK cyt olytic function in patients with SDAT than in healthy elders and in pa tients with dementia of multi-infarct origin (MID). This suppression i s completely lacking when cortisol is employed at low concentrations ( 10(-7) M) and is significantly reduced after incubation at physiologic al (10(-6) M; p < 0.001) and supraphysiological concentrations (10(-5) M; p < 0.001). The addition of IL-2 (50 and 100 IU/ml/cells) signific antly antagonizes the effects of cortisol in SDAT, whereas the cortiso l-dependent immunosuppression is partially maintained in healthy elder s and in patients with MID. Our data indicate that the defect of the i mmunosuppressive effect of cortisol may play a role in NK dysregulatio n in SDAT, contributing to the cytokine-mediated NK overactivity in th is disease.