Neostigmine modulates tularemia progression in BALB/c mice

Abstract

Neostigmine is a pseudo-irreversible inhibitor of enzyme acetylcholinesterase (AChE). We hypothesized link between neostigmine and cholinergic anti-inflammatory pathway via better availability of blood acetylcholine after AChE inhibition and consequent activation of nicotinic acetylcholine receptors. Owing to the expected mechanism of action, we expect significant impact of neostigmine on immunity. In the reported experiment, we used BALB/c mouse model and experimental infection with Francisella tularensis, a causative agent of tularemia. Interferon γ, interleukin 6 and mortality test are done for neostigmine doses of 8.00, 40.0 and 200 µg/kg. We proved significant decrease of both cytokines in course of neostigmine in a dose dependent manner. Neostigmine aggravates mortality caused by tularemia. Owing to the reported results, application of AChE inhibitors to patients suspected with tularemia or similar diseases can be considered as a life endangering therapy.