The acetylcholinesterase inhibitor, Donepezil, regulates a Th2 bias in Alzheimer's disease patients.
The increased pro-inflammatory cytokine production was previously observed in Alzheimer's disease (AD). We sought to explore whether acetylcholinesterase inhibitor (AChEI) therapy ameliorates clinical symptoms in AD through down-regulation of inflammation. Expression and release of monocyte chemotactic protein-1 (MCP-1), a positive regulator of Th2 differentiation, and interleukin (IL)-4, an anti-inflammatory cytokine from peripheral blood mononuclear cells (PBMC) in AD patients, were investigated. PBMC were purified from AD patients at time of enrollment (T0) and after 1 month of treatment with AChEI (T1) and from healthy controls (HC). Supernatants were analyzed for cytokine levels by ELISA methods. mRNA expression were determined by RT-PCR. Expression and production of MCP-1 and IL-4 were significantly increased in AD subjects under therapy with the AChEI Donepezil, compared to the same AD patients at time of enrollment (P < 0.001). Our data suggest another possible explanation for the ability of Donepezil [diethyl(3,5-di-ter-butyl-4-hydroxybenzyl)phosphonate] to delay the progression of AD; in fact, Donepezil may modulate MCP-1 and IL-4 production, which may reflect a general shift towards type Th0/Th2 cytokines which could be protective in AD disease. The different amounts of MCP-1 and IL-4 observed might reflect the different states of activation and/or responsiveness of PBMC, that in AD patients could be kept in an activated state by pro-inflammatory cytokines.
Reale
Marcella
M
Department of Oncology and Neuroscience, Unit of Immunology, University G. d'Annunzio, Via dei Vestini 31, 66123 Chieti, Italy. mreale@unich.it
Iarlori
Carla
C
Gambi
Francesco
F
Feliciani
Claudio
C
Isabella
Lucci
L
Gambi
Domenico
D
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000077265:Donepezil; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018418:Th2 Cells / Q000187:drug effects* / Q000473:pathology
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D002800:Cholinesterase Inhibitors; D007189:Indans; D010835:Phytohemagglutinins; D010880:Piperidines; D012333:RNA, Messenger; D015847:Interleukin-4; D000077265:Donepezil