Níveis séricos de lipopolissacarídeo (LPS) e sCD14 e associação com gravidade da leishmaniose visceral humana

Abstract

Visceral leishmaniasis (VL) is a severe disease caused by a protozoa of the genus Leishmania. The classic VL is characterized by a systemic infection of phagocytic cells and an intense activation of inflammatory response, with major clinical manifestations: hepatosplenomegaly, fever and edema, neutropenia, thrombocytopenia, and hypergammaglobulinemia. The presence of inflammatory mediators in sera, including IFN-γ and IL-12, theoretically could help to control the infection. However, it is well known that VL patients present an absence a Th1 response specific to leishmania antigen (IL-2 and IFN-γ). Instead, it is observed a production of Th2 and T regulatory cytokines, especially IL-10. It is also unclear why 90% of infected individuals do not develop the disease, while others develop the classical form and some evolve into a more severe form unresponsive to treatment. In this study, we took advantage of this spectrum of disease outcomes, and our objective was to associate the immune profile of individuals infected with Leishmania infantum chagasi with the development of disease and disease severity. Sera from patients with confirmed diagnosis for VL were evaluated for the presence of molecules, sCD14, FABP2, MIF and LPS, and compared with healthy controls and asymptomatic individuals. Our results show elevated sCD14 in VL patients as compared to asymptomatic individuals, without differences in LPS levels. This data suggest that some molecule from leishmania could be starting the activation of the inflammatory response via CD14, stimulating a generalized inflammatory response, with production of several cytokines and soluble molecules, including IFN-γ, IL-27, IL- 10, IL-6 and sCD14. These cytokines are strongly associated with hepatosplenomegaly, neutropenia and thrombocytopenia. We also observed that IL-6 levels greater than 200 pg/ml is strongly associated with death. Together our data reinforce the close relationship of IFN-γ, IL-10, IL-6, TNF-α and IL-27 in immune dynamics of VL and suggest the direct participation of sCD14 in the activation of the immune response against L. infantum chagasi.