Avaliação in vitro da atividade linfoproliferativa do metil galato frente a células mononucleares do sangue periférico (PBMC) de pacientes com Leishmaniose Cutânea

Abstract

American Tegumentary Leishmaniasis (ATL) is considered by the World Health Organization (WHO) as one of the most important Neglected Tropical Diseases (NTDs). Due to the limitations of current treatments for ATL, which include significant adverse effects and low availability in remote areas, the search for new therapeutic alternatives is essential. Natural products have shown promising results in experimental studies and are being explored as potential strategies for the treatment of leishmaniasis. In this study, biological samples were collected from 20 volunteers, including 10 patients with confirmed diagnosis of cutaneous leishmaniasis (CL), without prior treatment, living in the municipality of Rio Preto da Eva (AM), and 10 healthy individuals with no history of leishmaniasis, residents of Manaus (AM). Blood samples were used to obtain peripheral blood mononuclear cells (PBMCs), which were subjected to in vitro experiments with methyl gallate (MG). Analyses included the evaluation of lymphoproliferative responses and molecular characterization of Leishmania isolates from lesions by qPCR. In newly infected patients (Gr1), MG at 54 μg/mL induced an average lymphoproliferation of 30%, a value similar to that observed with Glucantime® (34%). The positive control with phytohemagglutinin (PHA) induced 92% response, confirming cell viability. In the control group/Gr2 (healthy volunteers), MG induced on average 51% of lymphoproliferation, Glucantime® 63%, and PHA 87%, with statistically significant differences among stimuli (p < 0.0001 for patients; p = 0.0102 for controls). Molecular characterization of biological isolates from the 10 CL patients revealed 100% of cases caused by Leishmania (Viannia) guyanensis. The results demonstrate that MG, at the tested concentration, presents moderate and relevant in vitro lymphoproliferative activity against PBMCs from CL patients and healthy volunteers, suggesting its potential ability to modulate immune mechanisms by stimulating a natural response in healthy individuals and even a specific (adaptive immune response) in CL patients. These findings support the potential of MG as a therapeutic alternative against ATL. This study highlights the importance of continuing research with the substance MG, emphasizing the need to characterize its immunomodulatory activity in human immune system cells through immunophenotyping and the analysis of cytokine expression levels, such as IL-2, IL-4, IL-10, IL-12, IFNɣ, TNFβ, and IL-17.