Effect of donepezil on innate antiviral immunity of human leukocytes

Abstract 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. NFκB 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 L 929 and A 549 cells was not shown. The effect was dose dependent and individually differentiated. The production of TNFα and IFNs was reduced in infected leukocytes in a dose-dependent manner in the PBLs of the healthy blood donors and of AD patients. NFκB activation was also reduced by donepezil. Conclusions Donepezil regulate two mechanisms of innate immunity of leukocytes: resistance to viruses and cytokine production.