Acetylcholinesterase inhibitors reduce brain and blood interleukin-1beta production.
Overproduction of interleukin-1 within the brain is associated with Alzheimer's disease and other neurological conditions. We report that peripheral administration of the acetylcholinesterase inhibitors tacrine, rivastigmine, neostigmine, or EN101 (an antisense oligonucleotide directed at acetylcholinesterase messenger RNA) to mice significantly attenuated the production of interleukin-1beta in the hippocampus and blood, concomitantly with the reduction in acetylcholinesterase activity. These findings demonstrate that cholinergic enhancement produces central and peripheral antiinflammatory effects and suggest a novel therapeutic mechanism for acetylcholinesterase inhibitors.
Pollak
Yehuda
Y
Department of Psychology, The Hebrew University of Jerusalem, Jerusalem, Israel.
Gilboa
Adi
A
Ben-Menachem
Ofra
O
Ben-Hur
Tamir
T
Soreq
Hermona
H
Yirmiya
Raz
R
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009388:Neostigmine / Q000494:pharmacology; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D048448:Phenylcarbamates / Q000494:pharmacology; D000068836:Rivastigmine; D013619:Tacrine / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; C477243:EN101; D007375:Interleukin-1; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D048448:Phenylcarbamates; D009388:Neostigmine; D013619:Tacrine; D000068836:Rivastigmine