Efeitos da estimulação colinérgica com brometo de priridostigmina na cardiopatia chagásica crônica em camundongos

Abstract

Although the pathogenesis of Chagas' disease is highly complex and not completely understood, it is widely accepted that a balance between the invasion of the parasite and the immune-inflammatory response of the host plays an important role in the development and progression of the disease. In recent years many studies in the literature has been highlighting the marked influence of the autonomic nervous system on the immune system in various experimental models of inflammatory diseases, whether infectious or autoimmune diseases, among others. This work had the object of investigation to assess the effects of changes in autonomic parasympathetic neuroimmunomodulation, employing the anti-cholinesterase pyridostigmine bromide on the experimental chronic Chagas' disease in mice. To this end, C57BL/6J mice controls (Con) non treated (NT), or treated with pyridostigmine bromide (Pyr) and C57BL/6J mice inoculated with trypomastigotes of Romildo strain, respectively, T. Cruzi (Chg) non treated (NT) or treated with pyridostigmine bromide (Pyr) were used. All animals were followed for 6 months and at the ending they were assessed for presence of blood and tissue parasites, conventional electrocardiogram (ECG) under anesthesia, study of cardiac autonomic function by means of analysis of heart rate variability and pharmacological autonomic blockade with atropine and propranolol, heart histopathology and quantification of cytokines: tumor necrosis factor-alpha (TNF-α), interferon gamma (IFNγ), interleukin 5 (IL- 5) and interleukin 10 (IL-10). At the end of the observation period it was observed a significant change in the electrocardiographic profile, autonomic and histopathological findings, suggestive of an inflammatory response with a shift of immune response towards the Th1 in Chg-NT animals compared to the other groups. It was observed that chronic treatment with anticholinesterase pyridostigmine bromide, in Chg-pyrido animals, caused a significant reduction in inflammatory immune response, myocardial fibrosis, without alteration of tissue and blood parasitism, suggesting a reduction in Th1 immune response without changing the Th2. This reduction in Th1 profile can be partly confirmed by a decrease in serum levels of IFNγ and tendency to decrease TNF-α, with no change in levels of IL-10, in Chg-pyrido animals when compared to NT-Chg group. In conclusion, our findings confirm the marked neuroimuno-modulatory role played by parasympathetic autonomic nervous system in the evolution of inflammatory-immune response to T. cruzi during the chronic Chagas' disease in experimental mice.