Tacrine can suppress immune response to tularemia in BALB/c mouse model

Abstract

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 µg/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-γ) 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.