What we could learn about Chagas´ disease from our experimental therapeutic trials

Sadí Cossy Isasi, Juan Carlos Muiño


Background: Chagas´ disease is an important endemic in Latin America, caused by the protozoan Trypanosoma cruzi (T. cruzi), presents irreversible autoimmune panmyocarditis in 24% of infected patients only in Argentina. We already reported lethally T. cruzi infected mice survival when treated with GM1 bovine brain ganglioside. Healthy IgGs anti-β adrenergic receptors (ABrs)become autoimmune in Chagas´ disease but in GM1 treatment it remains unclear. Since GM1 promotes Th2 response, it would be expected to worsen the fate of infected mice due to increased ABrs.

Methods: We analyze our results and selected literature to improve our understanding going along the “blade” of immunity-behavior. New experimental sets were: 80 mice divided into 2 groups: a) healthy control, b) healthy challenged with serum albumin (A);160 three months old outbreed Albino Swiss mice were divided into 4 groups: a) non-infected, b) survivors of infection with T. cruzi, 0.7´105 parasites c) infected with T. cruzi, 0.7´105 parasites and treated with GM1 0,1 mg /day by intramuscular injection for 30 days d) infected with T. cruzi, 0.7´105 parasites and treated with oral fluoxetine (F) 0,08 mg /day. Mice were tested at 120 days post treatment.  Another set of experiments comprised equal number of mice but GM1 was administered after F or vice versa. All mice of both sexes were subject of forced swimming test (FST).

Results: healthy mice showed climbing -adrenergic- dominance, chronic mice showed swimming and then floating, signs of progressive depression. “A” mice were swimmers but GM1 treated ones preserved the climber profile.

Conclusion: Considering depression (floating) is associated with inflammation, negotiation (swimming) with IgG production and reaction (climbing) with healing, we propose that the onset of infection shifted the immune metabolic frame from regulation through healthy IgGs anti-Brs to self-challenged through autoimmune IgGs anti-Brs,   and that process was partly reversed by GM1.


Chagas´disease, GM1, metabolism, autoimmunity, behavior, forced swimming test

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DOI: http://dx.doi.org/10.18103/imr.v6i1.844


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