OBJECTIVES: 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.
DESIGN: 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....