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Int. J. Mol. Sci. 2016, 17(12), 2009; doi:10.3390/ijms17122009

Dysregulated Homeostasis of Acetylcholine Levels in Immune Cells of RR-Multiple Sclerosis Patients

Department of Biology and Biotechnologies Charles Darwin, Research, Center of Neurobiology Daniel Bovet, Sapienza University of Rome, 00185 Rome, Italy
Department of Medical, Oral and Biotechnological Science, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
School of Hygiene and Preventive Medicine, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
Department of Neurology and Psichiatry, Sapienza University of Rome, 00185 Rome, Italy
Department of Neurosciences, San Camillo Forlanini Hospital, 00185 Rome, Italy
These authors equally contributed to this work.
Author to whom correspondence should be addressed.
Academic Editor: Christoph Kleinschnitz
Received: 24 September 2016 / Revised: 10 November 2016 / Accepted: 22 November 2016 / Published: 30 November 2016
(This article belongs to the Special Issue Advances in Multiple Sclerosis 2016)
View Full-Text   |   Download PDF [1349 KB, uploaded 30 November 2016]   |  


Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (ACh) contributes to the modulation of central and peripheral inflammation. We studied the homeostasis of the cholinergic system in relation to cytokine levels in immune cells and sera of relapsing remitting-MS (RR-MS) patients. We demonstrated that lower ACh levels in serum of RR-MS patients were inversely correlated with the increased activity of the hydrolyzing enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Interestingly, the expression of the ACh biosynthetic enzyme and the protein carriers involved in non-vesicular ACh release were found overexpressed in peripheral blood mononuclear cells of MS patients. The inflammatory state of the MS patients was confirmed by increased levels of TNFα, IL-12/IL-23p40, IL-18. The lower circulating ACh levels in sera of MS patients are dependent on the higher activity of cholinergic hydrolyzing enzymes. The smaller ratio of ACh to TNFα, IL-12/IL-23p40 and IL-18 in MS patients, with respect to healthy donors (HD), is indicative of an inflammatory environment probably related to the alteration of cholinergic system homeostasis. View Full-Text
Keywords: acetylcholine; acetylcholinesterase; butyrylcholinesterase; multiple sclerosis; cytokines acetylcholine; acetylcholinesterase; butyrylcholinesterase; multiple sclerosis; cytokines

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Di Bari, M.; Reale, M.; Di Nicola, M.; Orlando, V.; Galizia, S.; Porfilio, I.; Costantini, E.; D’Angelo, C.; Ruggieri, S.; Biagioni, S.; Gasperini, C.; Tata, A.M. Dysregulated Homeostasis of Acetylcholine Levels in Immune Cells of RR-Multiple Sclerosis Patients. Int. J. Mol. Sci. 2016, 17, 2009.

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