Tularemia Progression and it Modulation Including Mortality Remission and Enhancing of Immune System Response Using Asoxime (HI-6)

ABSTRACT Objective: Francisella tularensis is an intracellular pathogen causing tularemia disease. Immune system action against tularemia is limited due to lipopolysaccharide covering bacterial cell. Cholinergic anti-inflammatory pathway is a link between parasympathetic nervous system and macrophage assisted immunity. Asoxime (also known as HI-6) is a compound implicated in regulation of acetylcholinesterase as well as acetylcholine receptors. We hypothesize suitability of asoxime to modulate tularemia progression. Procedure and experiment design: Laboratory mice BALB/c were infected with F. tularensis LVS strain and challenged by application of 209 μg/kg to 209 mg/kg of HI-6 in the experiment beginning and then the next day. Mice were sacrificed after five days. Plasma, spleen and liver were sampled. In the separate experiment, tularemia caused mortality was assessed with and without of asoxime application. Results and Conclusions: Regarding to oxidative damage of liver and spleen, asoxime altered lipid peroxidation in liver and significantly reduced oxidative damage in spleens. We also proved significant increase of plasmatic antibodies level, decrease of IL6 and steady level of IFNg. Mice treated with asoxime had reduced mortality when compared to the infected and untreated ones. The best protective index was calculated 2.6 for asoxime doses 2.09 and 20.9 mg/kg. Asoxime can be considered as a compound reducing detrimental impact of tularemia. Effect of asoxime on cholinergic anti-inflammatory pathway and overall practical effect is discussed. Tularemia Progression and it Modulation Including Mortality Remission and Enhancing of Immune System Response Using Asoxime (HI-6)