Excitatory Pattern of Gamma-Interferon on Natural Killer Cell Activity in Senile Dementia of the Alzheimer Type

Abstract

Spontaneous natural killer (NK) cell activity and NK-induced cytotoxicity after interferon-γ (IFN-γ) were measured in healthy elderly subjects and in patients with senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID). Normal basal and IFN-γ-stimulated NK cytotoxicity were found in healthy old subjects and in patients with MID. On the contrary higher NK cytotoxicity after IFN-γ (650 IU) was demonstrated in SDAT patients than in MID and healthy subjects (p < 0.001). A significant inverse correlation between the percent increase of NK cytotoxicity after IFN-γ and the Mini Mental State Examination score (p < 0.001) was also demonstrated in patients with SDAT. Our data might suggest a cytokine-dependent mechanism of NK activation in SDAT associated with the neuroimmune hypothesis of the disease.

Dehydroepiandrosterone Sulfate Decreases the Interleukin-2-Mediated Overactivity of the Natural Killer Cell Compartment in Senile Dementia of the Alzheimer Type

“…NK cytotoxicity was normal in basal con- Solerte/Fioravanti/Schifino/Cuzzoni/ Fontana/Vignati/Govoni/Ferrari ditions (spontaneous lysis) and was physiologically stimulated after IL-2 incubation. These results confirmed our previous data related to the study of NK functional activity in healthy old people and demonstrated a similar pattern of NK cytotoxicity in healthy subjects of young and old age [50][51][52][53][54][55]. Concerning the in vitro effects of DHEAS, an increased cytotoxic response of NK cells was observed in healthy young subjects (mean percent increase 85%) and the amount of cytotoxicity after DHEAS exposure was similar to that found for IL-2 [50].…”

“…This evidence may be of great interest as regards the neuroimmune hypothesis of Alzheimer's disease [55][56][57][58][59][60][61]. In fact, the impaired NK cell response after DHEAS exposure (in particular after coincubation with IL-2) might contribute to reducing NK cell overactivity in SDAT [50][51][52][53][54][55], thereby decreasing one of the neuroimmune components of risk associated with SDAT neuropathology.…”

Decreased Immunosuppressive Effect of Cortisol on Natural Killer Cytotoxic Activity in Senile Dementia of the Alzheimer Type

“…These changes may be associated with the other abnormalities of NK cellular compartment Solerte/Cerutti/Severgnini/Rondanelli/ Ferrari/Fioravanti already suggested in SDAT [8][9][10][11]. In this context, we have reported several original aspects to the effects of cortisol incubation at different molar concentrations (physiological and nonphysiological) and during the concomitant activation of NK cytolytic function with IL-2 exposure.…”

“…In fact, in previous studies we have reported NK overactivity after IL-2, IFN-Á and IFN-ß exposure in patients with SDAT [8][9][10][11], also suggesting that NK dysregulation may be involved in the neuroimmune mechanism leading to neuropathology and neuronal loss [1][2][3][4][5][6][7]47]. The occurrence of a defect of the immunosuppressive effect of cortisol in SDAT may therefore provide important consequences in the clinical course of the disease, both influencing the progression of complications and of disability.…”

“…In this direction, our preliminary data have demonstrated an increased reactivity of natural killer (NK) cells to cytokines (i.e. IL-2, IFN-Á and IFN-ß) in patients with senile dementia of the Alzheimer type (SDAT) [8][9][10][11]. In these patients we have reported an enhanced NK cytotoxic activity after exposure to cytokines and an association between the NK dysregulation and the impairment of cognitive status.…”