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P‐095: Effect of donepezil on innate antiviral immunity of human leukocytes
Author(s) -
Leszek Jerzy W.,
Sochocka Marta,
Zaczyńska Ewa,
Błach-Olszewska Zofia
Publication year - 2007
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2007.04.348
Subject(s) - vesicular stomatitis virus , immunology , donepezil , immunity , innate immune system , proinflammatory cytokine , virology , medicine , virus , biology , inflammation , immune system , disease , dementia
Background: Peripheral blood leukocytes of Alzheimer Disease (AD) patients after donepezil therapy were previously found resistant to viral infection.These results contrasted with those obtained in control age group.The leukocytes were very sensitive to vesicular stomatitis virus (VSV) infection. Objective(s): In view of that donepezil effect on innate immunity reactions, i.e. production of cytokines and deficiency of resistance of ex vivo leukocytes to viral infections was studied. Methods: Results: ELISA test was used to determine the level of IFN-alfa, IFNgamma, TNF-alfa, and IL-10. Leukocyte resistance was determined by infection with VSV and study of kinetics of viral replication.NF-kB activation was measured by immunocytochemical method using anti-p65 antibodies (Chemicon). Donepezil (Pfizer) was used in nontoxic concentrations 10-50 ug/ml. Among healthy blood donors (n 30) two groups were distinguished: one with resistant leukocytes (n 15) and the second (n 15) with leukocytes sensitive to VSV.The resistant leukocytes produced about 10 times more cytokines than the sensitive ones, except IFN-alfa, which was produced by VSV-infected sensitive leukocytes only. Both groups differed also in cell percentage with constitutively activated NK-kB: 1523% in resistant, and 1-8% in sensitive leukocytes. Donepezil used in a concentration 10-50ug/ml reduced production of TNF-alfa in both groups, reduced production of IFN-alfa in sensitive cells, increased production of IL-10 and sometimes IFN-gamma in leukocytes producing these cytokines, but did not stimulate the cytokines. In the same concentration donepezil was able to stimulate resistance of leukocytes previously very sensitive to VSV. Conclusions: Donepezil exhibited two activities: ability to reduce TNF-alfa and IFN-alfa level, which may potentially be useful in a case of overproduction of these two cytokines in inflammatory, neurodegenerative and autoimmune disorders, and stimulation of leukocyte resistance, which may take advantage in viral diseases.