Pathogenesis of pancytopenia in canine visceral leishmaniasis

Abstract

Visceral leishmaniasis (VL) is a severe infectious disease that affects the mononuclear phagocytic system and may be lethal to the host. Pancytopenia is an important manifestation of the VL that may contribute to the letality if not treated. Thus, knowledge on the mechanisms involved in this process is very important, since their understanding may contribute to more efficient therapeutic intervention. Eventhough pancytopenia is considered a result of hypersplenism it is not clear which mechanisms are operating in this process. Studies have shown the importance of growth factors (Colony-Stimulating Factors) and some cytokines such as TNF-alfa in hematopoiesis in human patients with VL. Moreover, the insulin-like growth factor (Insulin-like growth factor - IGF)-I has been considered as a major promoter of growth of hematopoietic cells in vitro. In active VL low levels of IGF-I were observed compared to control. In this context, we will study the pathogenesis of pancytopenia in canine VL, considered a model of human disease, aiming at understanding the mechanisms of benefit in patients with active VL. The aim of this project is to analyze a possible contribution of low levels of IGF-I in pancytopenia in active LV, besides evaluation of alterations in the myelogram and the expression of GM-CSF, TNF-alfa, IL-3, IL-4, IL-7 and IL-11 in the bone marrow, other factors considered involved in hematopoiesis. We will evaluate these parameters in dogs naturally infected with Leishmania (Leishmania) chagasi and healthy dogs and in parallel in hamsters experimentally infected with L. (L.) chagasi (another good experimental model of LV) and uninfected hamsters.