Title

Physiologic modulation of natural killer cell activity as an index of Alzheimer's disease progression

Authors

Paolo Prolo^1,*, Francesco Chiappelli¹, Alberto Angeli², Andrea Dovio²,Paola Perotti², Marisa Pautasso³, Maria Luisa Sartori², Laura Saba², Stefano Mussino², Thomas Fraccalini⁴, Fausto Fantó⁴, Cristina Mocellini⁵, Maria Gabriella Rosso⁵, Enzo Grasso⁵

Affiliation

¹Division of Oral Biology & Medicine, UCLA School of Dentistry, Los Angeles, CA 90095-1668, West-Los Angeles, Veterans Administration Medical Center, Los Angeles, CA 90025; ²Internal Medicine, University of Turin, A.S.O. S. Luigi Gonzaga, Orbassano, Italy; ³Flow Cytometry Lab, University of Turin, A.S.O. S. Luigi Gonzaga, Orbassano, Italy; ⁴Geriatrics, University of Turin, A.S.O. S. Luigi Gonzaga, Orbassano, Italy; ⁵Neurology, A.S.O. S. Croce e Carle, Cuneo, Italy

Email

pprolo@dent.ucla.edu; * Corresponding author

Article Type

Current Trends

Date

received March 14, 2007; accepted March 20, 2006; published online March 21, 2007

Abstract

Patients with Alzheimer’s disease (AD) are characterized by an altered sensitivity to cortisol-mediated modulation of circulating lymphocytes. Longitudinal studies are needed to address the clinical applicability of these abnormalities as prognostic factors. Therefore, we designed a longitudinal study to address the clinical applicability of physiologic modulation of Natural Killer (NK) cell activity as a prognostic factor in AD. NK activity was assessed as baseline measurement and in response to modulation by cortisol at 10^-6M.  To verify the immunophysiological integrity of the NK cell population, we tested augmentation of NK cytotoxicity by human recombinant interleukin (IL)-2 (100 IU/ml) as control. The response to modulation by cortisol or by IL-2 was significantly greater in patients with AD. Based on change in the Mini-Mental State score at entry and at 18 months, patients with AD could be assigned to a “fast progression” (Δ > 2 points) or to a “slow progression” group (Δ < 2 points).  The change in the response of NK cytotoxic activity to cortisol, and the strength of the association of this parameter with circulating activated T cells in time was greater in patients with Fast Progression vs. Slow Progression AD. These results suggest that changes in the response of NK cells to negative (e.g., cortisol) or positive modifiers (e.g., IL-2) follow progression of AD.

Keywords

Alzheimer’s disease (AD); natural killer (NK) cells; NK cytotoxic activity; cortisol; interleukin (IL)-2; psychoimmunology

Citation

Edited by

P.Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.