Neglected diseases cause more than 534,000 deaths annually and is prevalent mostly in poor/developing countries. Leishmaniasis fit this frame and cause approximately 2.1 million DALYs (disability-adjusted life year), expressed as the number of years lost due to ill health, disability or early death. Among the various clinical forms that the disease presents, this it is being dependent on the parasite species, strain and host immune status. Visceral leishmaniasis (VL) is the most severe form of the disease, if untreated it´s fatal. The limited therapeutic tools available in the market for the VL treatment has several limitations, such as hepato, nephro and cardiotoxic effect. Often, the toxicity may be related to immune response induced by the drug, for example, high TNF-± production generated by the amphotericin B action, which despite their antiparasitic activity may lead to an exacerbated inflammation. In this context immunomodulatory drugs may be the key of treatment outcome. Thus, looking for new therapies, the study of drugs activity that are already on the market for other diseases, drug repositioning, has been promising for neglected diseases. Within this scenario, the objective of this project is to evaluate in vitro, the cellular immune response against synthetic drugs with anti-Leishmania (Leishmania) infantum activities (preliminary data), such as cyclobenzaprine (muscle relaxant), sertraline and amitriptyline (anti- depression). Thus, in addition to studies of anti-Leishmania activity and toxicity in mammalian cells, assays are conducted in macrophages previously infected with L. (L.) infantum and co-cultured with splenic lymphocytes. These cells will be treated with the drugs under study to investigate Th1, Th2 and Th17 interactions in treatment outcome in vitro by flow cytometry. The study of the cellular immune response elicited by anti-Leishmania drugs could contribute to the choice and design of more selective drugs, targeted for an effective control and modulation of Leishmania spp infection.
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