Effect of donepezil on innate antiviral immunity of human leukocytes.
BACKGROUND
The effect of donepezil on two mechanisms of innate immunity: leukocyte resistance to viral infection and cytokine production was studied.


METHODS
The degree of natural resistance of human peripheral blood leukocytes (PBLs) was determined by studying the kinetics of vesicular stomatitis virus (VSV) replication. A titer of 0-1 log TCID(50) indicated complete resistance, 2-3 log partial resistance, and >4 lack of resistance. Cytokine levels were determined with use of ELISA test. NFkappaB activation was assayed by immunocytochemical staining.


RESULTS
Preliminary study of VSV replication in the PBLs of Alzheimer's disease patients showed a high sensitivity to infection, except of PBL those under donepezil therapy. The PBL resistance stimulated us to study the effect of donepezil on innate immunity. Donepezil inhibited VSV replication in the leukocytes of healthy blood donors but influence on infection in L929 and A549 cells was not shown. The effect was dose dependent and individually differentiated. The production of TNFalpha and IFNs was reduced in infected leukocytes in a dose-dependent manner in the PBLs of the healthy blood donors and of AD patients. NFkappaB activation was also reduced by donepezil.


CONCLUSIONS
Donepezil regulate two mechanisms of innate immunity of leukocytes: resistance to viruses and cytokine production.
Sochocka
Marta
M
Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Zaczyńska
Ewa
E
Leszek
Jerzy
J
Siemieniec
Iwona
I
Błach-Olszewska
Zofia
Z
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D002461:Cell Line, Transformed; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology; D007189:Indans / Q000494:pharmacology*; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects* / Q000821:virology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology
D002800:Cholinesterase Inhibitors; D016207:Cytokines; D007189:Indans; D016328:NF-kappa B; D010880:Piperidines; D000077265:Donepezil