Key result
Treatment with G-CSF in a mouse model of chronic Chagas disease cardiomyopathy reduced heart inflammation, fibrosis, and parasite load, mediated by an increase in regulatory T cells.
Why the study?
Does G-CSF reduce inflammation, fibrosis, and parasite load in a mouse model of chronic Chagas disease cardiomyopathy?
Does G-CSF reduce inflammation, fibrosis, and parasite load in a mouse model of chronic Chagas disease cardiomyopathy?
In a mouse model of chronic Chagas cardiomyopathy, G-CSF reduces myocarditis and parasite load, associated with an increase in regulatory T cells.
Hypothesis-generating for G-CSF in Chagas cardiomyopathy; leaves open translation to human disease.
Chagas disease, caused by Trypanosoma cruzi infection, is a leading cause of heart failure in Latin American countries. In a previous study, we showed beneficial effects of granulocyte colony‐stimulating factor (G‐CSF) administration in the heart function of mice with chronic T. cruzi infection. Presently, we investigated the mechanisms by which this cytokine exerts its beneficial effects. Mice chronically infected with T. cruzi were treated with human recombinant G‐CSF (3 courses of 200 μg/kg/d for 5 d). Inflammation and fibrosis were reduced in the hearts of G‐CSF‐treated mice, compared with the hearts of vehicle‐treated mice, which correlated with decreased syndecan‐4, intercellular adhesion molecule‐1, and galectin‐3 expressions. Marked reductions in interferon‐γ and tumor necrosis factor‐α and increased interleukin‐10 and transforming growth factor‐β were found after G‐CSF administration. Because the therapy did not induce a Th1 to Th2 immune response deviation, we investigated the role of regulatory T (T reg ) cells. A significant increase in CD3 + Foxp3 + cells was observed in the hearts of G‐CSF‐treated mice. In addition, a reduction of parasitism was observed after G‐CSF treatment. Our results indicate a role of T reg cells in the immunosuppression induced by G‐CSF treatment and reinforces its potential therapeutic use for patients with Chagas disease.—Vasconcelos, J. F., Souza, B. S. F., Lins, T. F. S., Garcia, L. M. S., Kaneto, C. M., Smapaio, G. P., de Alcântara, A. C., Meira, C. S., Macambira, S. G., Ribeiro‐dos‐Santos, R., Soares, M. B. P., Administration of granulocyte colony‐stimulating factor induces immunomodulation, recruitment of T regulatory cells, reduction of myocarditis and decrease of parasite load in a mouse model of chronic Chagas disease cardiomyopathy. FASEB J. 27, 4691–4702 (2013). www.fasebj.org
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Vasconcelos et al. (2013) studied chronic Chagas disease cardiomyopathy. human recombinant G-CSF vs. vehicle was evaluated on Inflammation, fibrosis, and parasite load. Treatment with G-CSF in a mouse model of chronic Chagas disease cardiomyopathy reduced heart inflammation, fibrosis, and parasite load, mediated by an increase in regulatory T cells.
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