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 enrolment (T0) and after 1 month of treatment with AChEI (T1) and from healthy controls (HC). Supernatants were analyzed for cy- tokine levels by ELISA methods. mRNA expression were determined by RTePCR. Expression and production of MCP-1 and IL-4 were sig- nificantly increased in AD subjects under therapy with the AChEI Donepezil, compared to the same AD patients at time of enrolment (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.

The acetylcholinesterase inhibitor, Donepezil, regulates a Th2 bias in Alzheimer’s disease patients.

REALE, Marcella;GAMBI, Francesco;GAMBI, Domenico
2006-01-01

Abstract

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 enrolment (T0) and after 1 month of treatment with AChEI (T1) and from healthy controls (HC). Supernatants were analyzed for cy- tokine levels by ELISA methods. mRNA expression were determined by RTePCR. Expression and production of MCP-1 and IL-4 were sig- nificantly increased in AD subjects under therapy with the AChEI Donepezil, compared to the same AD patients at time of enrolment (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.
File in questo prodotto:
File Dimensione Formato  
neurophar..pdf

Solo gestori archivio

Tipologia: Documento in Post-print
Dimensione 219.6 kB
Formato Adobe PDF
219.6 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/113873
Citazioni
  • ???jsp.display-item.citation.pmc??? 14
  • Scopus 58
  • ???jsp.display-item.citation.isi??? 54
social impact