Alzheimer patients treated with an AchE inhibitor show higher IL-4 and lower IL-1 beta levels and expression in peripheral blood mononuclear cells.
The study evaluates the expression and production of cytokines in peripheral blood mononuclear cells of patients with Alzheimer disease treated or not treated with acetylcholinesterase inhibitor, which enhances neuronal transmission. Cytokines associated with brain inflammation such as interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha have been implicated in the regulation of amyloid peptide protein synthesis. The anti-inflammatory cytokine, IL-4, may suppress the activity of IL-1beta. Patients were assessed for clinical and immunologic features at baseline and after 1 month of treatment with Donepezil, an acetylcholinesterase inhibitor. Peripheral blood mononuclear cells were cultured with and without phytohemagglutinin stimulation. IL-1beta and IL-4 levels were measured by enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used to determine the expression of cytokines in peripheral mononuclear cells. Compared with untreated patients and healthy control subjects, IL-1beta levels and expression decreased in Alzheimer disease patients treated with Donepezil (P < 0.001). In contrast, IL-4 levels and expression were significantly higher in Alzheimer patients treated with the acetylcholinesterase inhibitor. This increment was observed in both unstimulated and phytohemagglutinin-stimulated peripheral blood mononuclear cells.
Gambi
Francesco
F
Psychiatry Unit, Department of Oncology and Neuroscience, University G. d'Annunzio, Via dei Vestini, 66013 Chieti, Italy. Gambi@unich.it
Reale
Marcella
M
Iarlori
Carla
C
Salone
Anatolia
A
Toma
Lucia
L
Paladini
Carlo
C
De Luca
Giovanna
G
Feliciani
Claudio
C
Salvatore
Mirella
M
Salerno
Rosa M
RM
Theoharides
Theoharis C
TC
Conti
Pio
P
Exton
Michael
M
Gambi
Domenico
D
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000188:drug therapy / Q000201:enzymology; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use
D002800:Cholinesterase Inhibitors; D007189:Indans; D007375:Interleukin-1; D010880:Piperidines; D015847:Interleukin-4; D000077265:Donepezil