Análise da Correlação entre Citocinas da Medula Óssea, Carga Parasitária e Características Clínico-Laboratoriais na Leishmaniose Visceral Humana Grave

Abstract

Visceral Leishmaniasis (VL) is a systemic disease, and can be fatal if left untreated. In Brazil, it occupies an important epidemiological role and, currently, it is urbanized and in rapid expansion. In spite of the intensive treatment resources and established routines for the specific treatment of VL, an increase in lethality of the disease has been observed in several regions of the country. Since its development or control depends on the efficacy of host immune responses and the ability of the parasite in order to escape this response, the understanding of immunopathological mechanisms may contribute to the early identification of patients with a higher risk of unfavorable outcome, and, consequently, reduce lethality. Factors that determine the progression to the severe form of the disease have not yet been fully identified, but a cellular immune response specific for leishmaniasis appears to play a key role. In VL, the immune system is highly activated with production of cytokines and growth factors, for example, insulin-like growth factor I (IGF-1). In addition, there is a fine line between immune responses that effectively control parasite growth and induce long-term immunity from those that allow parasite persistence and associated disease. The study verified the immune response through cytokines, IGF-I and parasite load in the bone marrow of individuals with VL. The results showed a high non-dichotomized production (Th1 and Th2) of cytokines and there was no significant difference in the expression of IFN-γ TNF-α, IL-10, IL-6, IL-12p40 and IGF-I among the severity of VL; although the severe group presented worse mean in the peripheral laboratory parameters. Although IFN-γ is involved in parasite control and is found at increased levels in patients with VL, its ability to exert this function appears to be suppressed by IL-10, which can be observed by the strong and negative correlation between IFN-γ and IL-10 levels observed in the study. We also found a nonsignificant relationship between spinal cord load and the severity of individuals with VL and a weak correlation between parasite load and IGF-I expression. There was no difference between the IGF-I marrow gene expression between the active and control VL individuals and the low correlation of this growth factor with the IFN-γ TNF-α, IL-10, IL-6, IL-03 and CSF2 cytokines. The understanding of the immunopathogenesis of the disease in the bone marrow environment through measurements of immunological markers (cytokines and growth factor) that participate in the clinical progression of the disease can help prevent an unfavorable situation and subsidize the development of new therapies.