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publicado em 02/02/2013 às 11h00:00
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Research opens way for treating myocarditis induced Chagas disease

 
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One of the most serious sequelae of Chagas disease is heart disease caused by chronic inflammation of the heart muscle - myocarditis - which slowly destroys the body. Research recently completed at the Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP-USP), helped to better understand the involvement of the immune system in the process, paving the way for new treatments.

According to the results published in the journal PLoS Neglected Tropical Diseases, two types of lymphocytes - regulatory T cells (Treg) and T helper cells or helper 17 (Th17) - are primarily responsible for modulating the intensity of the attack the parasite that causes the disease : Trypanosoma cruzi.

When these lymphocytes are reduced in the body of the host, the attack on T. cruzi is more intense and hence the aggression of the heart's own immune system is also higher. Since patients with Chagas disease with higher amounts of circulating Treg and Th17 have a better prognosis and an asymptomatic chronic phase of the disease.

In mice infected with T. cruzi, we show that if the function of these cells is inhibited, the animal dies as a result of myocarditis. But when the activity of these cells is exacerbated too bad, because the body can not control the multiplication of parasites. These cells are necessary, but in the right amount, said João Santana Silva, USP professor and coordinator of the research supported by FAPESP.

Subsequently, based on the analysis of blood samples of patients with Chagas' disease, scientists have realized that also in humans there is a clear relationship between the amount of Treg and Th17 current and severity of myocarditis.

Based on this knowledge, it is possible to predict which asymptomatic patients are more likely to develop heart disease. The discovery also opens the way for the development of drugs capable of increasing the production of Treg and Th17 cells and modulate the immune response, said.

<b> 20 million people infected </ b>

The disease is the leading cause of myocarditis. According to data from Fiocruz, it is estimated that there are approximately 20 million patients infected in Latin America. Between 25% and 35% should develop cardiovascular changes.

According to Silva, it was believed in the past that there was no need to treat asymptomatic Chagas disease, because the main drug used against the parasite - benznidazole - causes severe side effects and is contraindicated in many cases. Furthermore, the benefits of treatment were not well defined.

Recent studies, however, show that all patients with Chagas evolve, although very slowly to the heart. The speed of the degenerative process will depend on the production of Th17 and Treg cells, explained Silva.

The disease is the leading cause of myocarditis. According to data from Fiocruz, it is estimated that there are approximately 20 million patients infected in Latin America.

These cells, like other lymphocytes, are produced in the bone marrow and comprise the group of so called white blood cells. Until recently, they were known only two types of T helper cells: Th1 and Th2 to. Recently it was discovered that there are several other types, the most important Treg and Th17. When the Thematic Project began, little was known about the role of these newly discovered cells, said Silva.

Once activated by contact with the pathogen, explained researcher, helper T cells produce a number of mediators that activate other types of leukocytes and trigger a specific immune response against the antigen.

Th17 cells are involved in autoimmune diseases, including arthritis and diabetes. Therefore, it was believed that their presence in the body was correlated with poor prognosis. In our research, however, we saw that the infection by T. cruzi and leishmaniasis, it is benign. It works in partnership with the Treg to curb harmful immune response, Silva said.

The production of Treg and Th17 may be influenced by genetic factors, previous diseases, food and the intestinal microbiota, explained Silva. In the case of Chagas disease, the interaction with the parasite is also a determining factor. In mice we found that some strains of the parasite stimulates more production of these cells. This is determined early in the infection, he said.

Veja mais detalhes da pesquisa no artigo Deficient Regulatory T Cell Activity and Low Frequency of IL-17-Producing T Cells Correlate with the Extent of Cardiomyopathy in Human Chagas' Disease.

<i> information Fapesp </ i>

Source: Isaude.net
   Palavras-chave:   Chagas disease    Myocarditis    USP    University of São Paulo    Ribeirão Preto   
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