SUMMARY
Tacrine is an inhibitor of enzyme acetylcholinesterase (AChE). In the past, it was used for the treatment of cognitive dysfunction during vascular
dementia and Alzheimer disease. Some works have concluded that AChE inhibitors can modulate immune response, and for this reason, we decided to
investigate the immune response to a model bacterial disease - tularemia - for which both innate and specific immunity are necessary to resolve the
disease. We used 64 BALB/c mice divided into eight groups exposed variously to saline, tacrine in a dose of 20.0-500 microg/kg, infection with
tularemia and infection with the contemporary application of tacrine. The mice were euthanized three days after the start of the experiment. We proved
a significant reduction in the levels of interleukin-6 (IL-6) and interferon gamma (IFN-gamma) in a dose response manner in the infected animals in
the course of tularemia. Moreover, tacrine caused a significant increase of the bacterial burden in the liver and spleen. We can conclude that tacrine
can aggravate tularemia: that it increases the accessibility of acetylcholine and in this way stimulates the cholinergic anti-inflammatory pathway.
The results represent a substantial contribution to the field of inflammation control in the nervous system and it is an advancement of the
inflammatory therapy issue.
KEY WORDS
inflammation; infection; Alzheimer disease; tacrine; acetylcholinesterase; innate immunity
REFERENCES
Ahmed M, Rocha JBT, Correa M, Mazzanti CM, Zanin RF, Morsch ALB, Morsch VM, Schetinger MRC. Inhibition of two different cholinesterases by tacrine.
Chem-Biol Interact. 162: 165-171, 2006.
[CrossRef]
[PubMed]
Alfirevic A, Mills T, Carr D, Barratt BJ, Jawaid A, Sherwood J, Smith JC, Tugwood J, Hartkoorn R, Owen A, Park KB, Pirmohamed M. Tacrine-induced liver
damage: an analysis of 19 candidate genes. Pharmacogenet Genomics. 17: 1091-1100, 2007.
[CrossRef]
[PubMed]
Carr DF, Alfirevic A, Tugwood JD, Barratt BJ, Sherwood J, Smith J, Pirmohamed M, Park BK. Molecular and genetic association of interleukin-6 in
tacrine-induced hepatotoxicity. Pharmacogenet Genomics. 17: 961-972, 2007.
[CrossRef]
[PubMed]
Chatterjee PK, Yeboah MM, Dowling O, Xue XY, Powell SR, Al-Abeb Y, Metz CN. Nicotinic Acetylcholine Receptor Agonists Attenuate Septic Acute Kidney
Injury in Mice by Suppressing Inflammation and Proteasome Activity. PLoS One. 7, 2012.
Chiavolini D, Alroy J, King CA, Jorth P, Weir S, Madico G, Murphy JR, Wetzler LM. Identification of immunologic and pathologic parameters of death
versus survival in respiratory tularemia. Infect Immun. 76: 486-496, 2008.
[CrossRef]
[PubMed]
Davis KL, Thal LJ, Gamzu ER, Davis CS, Woolson RF, Gracon SI, Drachman DA, Schneider LS, Whitehouse PJ, Hoover TM, Morris JC, Kawas CH, Knopman DS,
Earl NL, Kumar V, Doody RS. A double-blind, placebo-controlled multicenter study of tacrine for Alzheimers-disease. N Engl J Med. 327: 1253-1259,
1992.
[CrossRef]
[PubMed]
Fernandes-Alnemri T, Yu JW, Juliana C, Solorzano L, Kang S, Wu JH, Datta P, McCormick M, Huang L, McDermott E, Eisenlohr L, Landel CP, Alnemri ES. The
AIM2 inflammasome is critical for innate immunity to Francisella tularensis. Nat Immunol. 11: 385-394, 2010.
[CrossRef]
[PubMed]
Field RH, Gossen A, Cunningham C. Prior pathology in the basal forebrain cholinergic system predisposes to inflammation-induced working memory
deficits: reconciling inflammatory and cholinergic hypotheses of delirium. J Neurosci. 32: 6288-6294, 2012.
[CrossRef]
[PubMed]
Friedman A, Kaufer D, Shemer J, Hendler I, Soreq H, TurKaspa I. Pyridostigmine brain penetration under stress enhances neuronal excitability and
induces early immediate transcriptional response. Nat Med. 2: 1382-1385, 1996.
[CrossRef]
[PubMed]
Gnatek Y, Zimmerman G, Goll Y, Najami N, Soreq H, Friedman A. Acetylcholinesterase loosens the brain’s cholinergic anti-inflammatory response and
promotes epileptogenesis. Front Mol Neurosci. 5: 66, 2012.
[CrossRef]
[PubMed]
Jokanovic M. Medical treatment of acute poisoning with organophosphorus and carbamate pesticides. Toxicol Lett. 190: 107-115, 2009.
[CrossRef]
[PubMed]
Knapp MJ, Gracon SI, Davis CS, Solomon PR, Pendlebury WW, Knopman DS. Efficacy and safety of high-dose tacrine - a 30 week evaluation. Alzheimer Dis
Assoc Dis. 8: S22-S31, 1994.
Krall WJ, Sramek JJ, Cutler NR. Cholinesterase inhibitors: A therapeutic strategy for Alzheimer disease. Ann Pharmacother. 33: 441-450, 1999.
[CrossRef]
[PubMed]
Mahawar M, Atianand MK, Dotson RJ, Mora V, Rabadi SM, Metzger DW, Huntley JF, Harton JA, Malik M, Bakshi CS. Identification of a Novel Francisella
tularensis Factor Required for Intramacrophage Survival and Subversion of Innate Immune Response. J Biol Chem. 287: 25216-25229, 2012.
[CrossRef]
[PubMed]
Novosad J, Holicka M, Novosadova M, Krejsek J, Krcmova I. Rapid onset of ICAM-1 expression is a marker of effective macrophages activation during
infection of Francisella tularensis LVS in vitro. Folia Microbiol (Praha). 56: 149-154, 2011.
[CrossRef]
[PubMed]
Pohanka M. Alzheimer’s disease and related neurodegenerative disorders: implication and counteracting of melatonin. J Appl Biomed. 9: 185-196,
2011a.
[CrossRef]
Pohanka M. Cholinesterases, a target of pharmacology and toxicology. Biomed Pap. 155: 219-229, 2011b.
[CrossRef]
Pohanka M. Acetylcholinesterase inhibitors: a patent review (2008 - present). Expert Opin Ther Pat. 22: 871-886, 2012a.
[CrossRef]
[PubMed]
Pohanka M. Alpha7 nicotinic acetylcholine receptor is a target in pharmacology and toxicology. Int J Mol Sci. 13: 2219-2238, 2012b.
[CrossRef]
[PubMed]
Pohanka M, Pavlis O. Neostigmine modulates tularemia progression in BALB/c mice. Afr J Pharm Pharmacol. 6: 1317-1322, 2012.
[CrossRef]
Pohanka M, Pavlis O, Ruttkay-Nedecky B, Sochor J, Sobotka J, Pikula J, Adam V, Kizek R. Tularemia progression accompanied with oxidative stress and
antioxidant alteration in spleen and liver of BALB/c mice. J Microbiol. 50: 401-408, 2012.
[CrossRef]
[PubMed]
Shen H, Harris G, Chen W, Sjostedt A, Ryden P, Conlan W. Molecular immune resposnes to aerosol challenge with Francisella tularensis in mice
inoculated with live vaccine candidates of varying efficacy. PLoS One. 5: e13349, 2010.
[CrossRef]
[PubMed]
Sun L, Zhang GF, Zhang X, Liu Q, Liu JG, Su DF, Liu C. Combined administration of anisodamine and neostigmine produces anti-shock effects: involvement
of alpha 7 nicotinic acetylcholine receptors. Acta Pharmacol Sin. 33: 761-766, 2012.
[CrossRef]
[PubMed]
Teltingdiaz M, Lunte CE. Distribution of tacrine across the blood-brain-barrier in awake, freely moving rats using in vivo microdialysis
sampling Pharm Res. 10: 44-48, 1993.
[CrossRef]
Tyagi E, Agrawal R, Nath C, Shukla R. Effect of anti-dementia drugs on LPS induced neuroinflammation in mice. Life Sci. 80: 1977-1983, 2007.
[CrossRef]
[PubMed]
Wang J, Chen F, Zheng P, Deng WJ, Yuan J, Peng B, Wang RC, Liu WJ, Zhao H, Wang YQ, Wu GC. Huperzine A ameliorates experimental autoimmune
encephalomyelitis via the suppression of T cell-mediated neuronal inflammation in mice. Exp Neurol. 236: 79-87, 2012.
[CrossRef]
[PubMed]
Wilund KR, Rosenblat M, Chung HR, Vokova N, Kaplan M, Woods JA, Aviram M. Macrophages from alpha 7 nicotinic acetylcholine receptor knockout mice
demonstrate increased cholesterol accumulation and decreased cellular paraoxonase expression: a possible link between the nervous system and
atherosclerosis development. Biochem Biophys Res Commun. 390: 148-154, 2009.
[CrossRef]
[PubMed]
Zitnik RJ. Treatment of chronic inflammatory diseases with implantable medical devices. Cleve Clin J Med. 78: S30-S34, 2011.
[CrossRef]
[PubMed]
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