This work aimed at investigating the lipid profile of zoonotic visceral leishmaniasis (VL) patients' sera and the effect of lipoproteins on the in vitro production of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-10 and IL-12 by Leishmania infantum-infected and uninfected macrophages. Lipids were quantified in 26 VL patients' sera and 26 healthy controls from a VL endemic area. The patients' sera had higher triglyceride and very low density lipoprotein (VLDL) levels, and much lower apolipoprotein A1, total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) levels than the control sera. Lipoprotein fractions were obtained by ultracentrifugation of sera. The addition of LDL and HDL to Leishmania-infected and uninfected macrophages, in physiological concentrations, enhanced the production of IL-6 and IL-10, but not of IL-12. LDL stimulated the production of TNF-alpha only in infected macrophages, whereas HDL stimulated the production of lower amounts of TNF-alpha in both infected and uninfected macrophages. VLDL stimulated only the production of IL-10. It is proposed herein that LDL may influence the development of VL by promoting the production of TNF-alpha by infected macrophages. A decrease in plasma LDL in some VL patients (to 20 mg/mL or less); however, would tend to reduce the production of TNF-alpha and therefore to limit the development of immune-mediated pathology, not withstanding the fact that it would perhaps increase the permissiveness of macrophages to Leishmania growth.

Mammalian protection against leishmanial infection depends on the development of an effective immune response. Zoonotic visceral leishmaniasis (ZVL) patients are usually unable to mount an effective immune response against the parasite and indeed appear to be severely immunosuppressed. This suppression has strong nonspecific and specific components mediated by serum factors and leishmanicidal activity of infected macrophages, respectively. The lipid profile has been shown to be altered in ZVL patients' sera. This work aimed at (i) determining the HDL, Apo A1, LDL, and VLDL concentrations in ZVL patients' sera; (ii) investigating the oxidative effect of ZVL patients' sera on the β-carotene matrix; (iii) measuring IL-10, IL-6, IL-12p40, and tumour necrosis factor-α (TNF-α) concentrations in the macrophage cultures, to which 10% of ZVL patients' serum had been added. Levels of HDL, LDL fraction, and apolipoprotein A1 in ZVL patients' sera were lower than those of healthy individuals' sera, except for the mean level of VLDL. The matrix of β-carotene and linoleic acid system was oxidized in the presence of ZLV patients' sera. The presence of ZVL patients' sera did not modify the cytokine production of IL-6, IL-12p40, and IL-10 by human macrophages in vitro but TNF-α production was altered, probably due to lack of macrophage stimulation by lipoprotein.