Acetylcholinesterase inhibitors reduce brain and blood interleukin-1β 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-1 beta 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.