Abstract
BackgroundTrypanosoma cruzi is the causative agent of Chagas disease, which is endemic to subtropical and tropical Americas. The disease treatment remains partially ineffective, involving therapies directed to the parasite as well as palliative strategies for the clinical manifestations. Therefore, novel candidates for disease control are necessary. Additionally, strategies based on parasite inhibition via specific targets and application of compounds which improve the immune response against the disease is welcomed. Ghrelin is a peptide hormone pointed as a substance with important cardioprotective, vasodilatory, anti-apoptotic, anti-oxidative and immune modulatory functions. The aims of this study were to evaluate the immunomodulatory effects of ghrelin in male Wistar rats infected with the Y strain of T. cruzi.MethodsIn order to delineate an immune response against T. cruzi mediated by ghrelin, we evaluated the following parameters: quantification of blood and cardiac parasites; analysis of cell markers (CD3+, CD8+, NK, NKT, CD45RA+, macrophage and RT1B+); nitric oxide (NO) production; lymphoproliferation assays; splenocyte apoptosis; and INF-γ, IL-12 and IL-6 quantification in sera.ResultsThe animals infected with T. cruzi and supplemented with ghrelin demonstrated an upregulated pattern in macrophage and NO production, whereas an anti-inflammatory response was observed in T cells and cytokines. The low response against T. cruzi mediated by T cells probably contributed to a higher colonization of the cardiac tissue, when compared to infected groups. On the other side, the peptide decreased the inflammatory infiltration in cardiac tissue infected with T. cruzi.ConclusionsGhrelin demonstrated a dual function in animals infected with T. cruzi. Further studies, especially related to the decrease of cardiac tissue inflammation, are needed in order to determine the advantages of ghrelin supplementation in Chagas disease, mostly for populations from endemic areas.
Highlights
Trypanosoma cruzi is the causative agent of Chagas disease, which is endemic to subtropical and tropical Americas
Ghrelin decreased the weight of animals The ghrelin supplementation significantly decreased (ANOVA: F(3, 19) = 12.96, P < 0.0001) the weight of infected (IG) and non-infected (CG) animals, compared to the control or the infected groups (Fig.1)
Macrophage analysis and nitric oxide quantification The macrophage subset was not altered in animals infected with T. cruzi and/or supplemented with ghrelin (Fig. 2a)
Summary
Trypanosoma cruzi is the causative agent of Chagas disease, which is endemic to subtropical and tropical Americas. Strategies based on parasite inhibition via specific targets and application of compounds which improve the immune response against the disease is welcomed. Ghrelin is a peptide hormone pointed as a substance with important cardioprotective, vasodilatory, anti-apoptotic, anti-oxidative and immune modulatory functions. Chagas disease is a tropical neglected disease caused by Trypanosoma cruzi. One of the control strategies is based on the administration of molecules related to immune modulation, which contributes to an effective response against the parasite or avoid the deleterious symptoms of the chronic phase. Ghrelin is a hormonal peptide produced in ghrelinergic cells in the gastrointestinal tract and performs an important role in the regulation of appetite and metabolism [8, 9]. The peptide stimulates the AMP-activated protein kinase (AMPK) in the hypothalamus, improving the glucose uptake, the fatty acid oxidation, glycolysis, whereas inhibits the fatty acid and glycogen synthesis and gluconeogenesis [10, 11]
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