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

Solerte, Sebastiano Bruno; Cerutti, Nadia; Severgnini, S.; Rondanelli, Mariangela; Ferrari, Ettore; Fioravanti, Marisa

doi:10.1159/000017040

Cited by 12 publications

(6 citation statements)

References 34 publications

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“…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].…”

Section: Discussionsupporting

confidence: 90%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Solerte¹,

Fioravanti²,

Schifino³

et al. 1998

Dement Geriatr Cogn Disord

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Since dehydroepiandrosterone sulfate (DHEAS) has been involved in the regulation of cellular immunity, the aim of the presence study was to evaluate whether the age-dependent reduction of DHEAS was associated with changes of natural killer (NK) immune function in healthy elderly subjects and in patients with senile dementia of the Alzheimer type (SDAT). Circulating DHEAS 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 IU) coincubated with DHEAS (10^–7 M). DHEAS was significantly reduced in healthy elderly subjects (mesor M ± SD = 2.3 ± 0.5 µmol/l) and SDAT (1.6 ± 0.4 µmol/l) patients compared to healthy young subjects (6.7 ± 0.9 µmol/l; p < 0.001); significant differences were also found when healthy elderly subjects and SDAT patients were compared (p < 0.01). A significant inverse correlation between age and DHEAS levels was demonstrated in SDAT and healthy elderly subjects (p < 0.05). The decrease in 24-hour DHEAS secretion was associated with a higher NK cytotoxic response to DHEAS in the healthy elderly 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 DHEAS 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 physiological aging and SDAT. The antagonizing effect of DHEAS on NK overactivity during exposure with cytokines might counteract some neuroimmune components related to the pathogenesis and progression of the disease.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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

Solerte¹,

Fioravanti²,

Schifino³

et al. 1998

Dement Geriatr Cogn Disord

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“…Thus, it seems that microenvironment milieu in CNS of AD patients is a critical factor that may modulate the NK cells function. On the other hand, it has been demonstrated that not only NK cells in AD patients are sensitive to stimulation by cytokines such as IL‐2 or IFN‐γ [27], but also they are resistant to immunosuppressive effects of some drugs such as cortisol [27, 33]. Solerte et al.…”

Section: Nk Cell and Alzheimermentioning

confidence: 99%

The Role of Natural Killer Cells in Alzheimer’s Disease

et al. 2012

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive dysfunction and selective neuronal death in the brain. The aetiology of AD is not clear but environmental factors and heritable predisposition may play a role in the disease emergence. It has also been suggested that neural–immune interaction has a role in disease appearance. However, the underlying mechanisms are still unknown. Natural killer (NK) cells play an important role in the host defence, which is related to their ability to secrete a variety of cytokines and chemokines, as well as killing infected host cells. Moreover, there is some evidence that imply the involvement of NK cells in immunopathogenesis of AD. In this review, we have attempted to clarify the role of NK cells in the immunopathogenesis of AD.

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“…8 We have previously found that NK cells could be abnormally activated in old patients with dementia of the Alzheimer's type (DAT), suggesting a link between NK dysregulation and the neuroimmune mechanism of neurodegeneration. 9‐14…”

Section: Introductionmentioning

confidence: 99%

Overproduction of IFN‐γ and TNF‐α from Natural Killer (NK) Cells Is Associated with Abnormal NK Reactivity and Cognitive Derangement in Alzheimer's Disease

Solerte

Cravello

Ferrari

et al. 2000

Annals of the New York Academy of Sciences

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A BSTRACT : Alterations of natural killer (NK) function can be involved in the neuroimmune mechanism of neurodegeneration in dementia of the Alzheimer's type (DAT). NK cell cytotoxicity (NKCC) and the generation and release of IFN-␥ and TNF-␣ (spontaneous and modulated by IL-2) from pure NK cells (CD 16 +, CD 56 +, CD 3 -) were studied together with circulating IFN-␥ and TNF-␣ levels and cognitive function in 22 old patients with DAT and 15 healthy old subjects. Higher ( p < 0.001) IL-2 modulated NKCC (with IL-2 50 U/mL and 100 U/mL) was demonstrated in DAT patients (+ 35% and + 99% from baseline) than in healthy subjects (+ 6% and + 76% from baseline). Increased spontaneous and IL-2-induced release of IFN-␥ and TNF-␣ from NK cells were found in DAT patients compared to healthy subjects ( p < 0.001), whereas no difference of serum IFN-␥ and TNF-␣ was demonstrated between DAT and control groups. Significant negative correlations among the spontaneous release of IFN-␥ and TNF-␣ from NK and the decrease of the score of cognitive function (MMSE) were found in patients with DAT. In conclusion, alterations of NKCC control and NK-derived cytokine release in DAT could be involved in the neuroinflammatory mechanism related to the progression of neurodegeneration and dementia.

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

Cited by 12 publications

References 34 publications

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

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

The Role of Natural Killer Cells in Alzheimer’s Disease

Overproduction of IFN‐γ and TNF‐α from Natural Killer (NK) Cells Is Associated with Abnormal NK Reactivity and Cognitive Derangement in Alzheimer's Disease

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