title: Tacrine alters antibodies level in Francisella tularensis-infected mice.
abstract: OBJECTIVE
  Tacrine is an inhibitor of acetylcholinestrase (AChE) formerly used to treat cognitive impairment of Alzheimer disease. In previous works, we have shown that inhibitors of AChE can modulate innate immunity responses. In the present study we focused on modulation of adaptive immunity represented by production of antibodies. It is hypothesized that the cholinergic anti-inflammatory pathway is a common mechanism how inhibitors of AChE can influence immunity. Here, tularemia is used as a model disease for experimental purposes.
  
  
  METHODS
  A total of 64 BALB/c mice were divided into eight groups. The animals received a dose of tacrine 0.1-0.5 mg/kg with combination of saline or inoculum of Francisella tularensis. The doses of tacrine were derived from clinical trials. The animals were sacrificed after three days and total antibodies in plasma and bacterial burden in the liver were measured.
  
  
  RESULTS
  Tacrine did not alter the antibodies level in non-infected animals. Antibodies levels of infected animals administered tacrine were reduced in a dose response manner. Tacrine also caused an increase in total bacteria numbers in the liver.
  
  
  CONCLUSIONS
  Tacrine significantly suppressed adaptive immunity represented by the ability of the organism to produce antibodies. We infer that tacrine can modulate the cholinergic anti-inflammatory pathway by a mechanism based on inhibition of blood AChE followed by higher availability of acetylcholine. The anti-inflammatory pathway is then stimulated and the body is not able to simply resolve antigen. Application of an AChE inhibitor during infectious diseases can have detrimental consequences for the immune system.
authors.affiliation: Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic. miroslav.pohanka@gmail.com.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Pohanka
authors.affiliation: Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
authors.forename: Oto
authors.initials: O
authors.lastname: Pavlis
authors.affiliation: Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences Brno, Czech Republic. miroslav.pohanka@gmail.com.
authors.forename: Jiri
authors.initials: J
authors.lastname: Pikula
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000917:Antibody Formation / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005604:Francisella tularensis / Q000187:drug effects / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D013619:Tacrine / Q000494:pharmacology*; D014406:Tularemia / Q000276:immunology* / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D002800:Cholinesterase Inhibitors; D013619:Tacrine