In vivo and in vitro cytokine profiles and mononuclear cell subsets in Sicilian patients with active visceral leishmaniasis.

Sera from Sicilian patients with confirmed visceral leishmaniasis (Leishmania donovani infantum) were analysed at the moment of the diagnosis, during the course of the disease and after clinical recovery, for the concentration of IL-10, IFN-gamma, IL-4 and IL-2. The results show high concentrations of IL-10 and IFN-gamma in the sera at the beginning of infection that return to the normal range following successful chemotherapy. By contrast, PBMC stimulated in vitro with Ag and mitogen produced low levels of IL-10 and IFN-gamma when collected at the time of the diagnosis and normal levels when assayed after recovery. IL-2 was undetected in the sera and was significantly reduced in the supernatants of actively infected patients, returning to the normal level after recovery. IL-4 was absent in the sera and in high concentrations in the supernatants in all the phases of the disease. The levels of CD4+ and CD8+ T cells were within the normal range, but acute VL patients had markedly reduced levels of memory T cells (CD3+/CD45RO+) compared with healthy controls. These cells returned to the normal levels following successful chemotherapy. T cells are strongly activated in acute VL patients as indicated by the elevated number of CD3+ HLA-DR+ and by the increase in HLA-DR antigen on these cells. There was a significant reduction in the cell membrane DR antigen of the monocytes (CD 14+) during the acute phase of the disease, but it returned to the normal range after clinical recovery. These findings therefore suggest that in Sicilian patients with active VL the cytokine profile is not clearly characterized by Th2 phenotype as in mice, and both Th1-like and Th2-like cells appear to proliferate and to be activated. Furthermore, IL-10, rather than IL-4, could play an important part in the inhibition of IFN-gamma-induced macrophage activation and could reflect the levels of HLA-DR antigen expressed by the monocytes.