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 (Lei shmania donovani infantum) were analysed at the moment of the diagnosi s, during the course of the disease and after clinical recovery, for t he 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 beginnin g of infection that return to the normal range following successful ch emotherapy. 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 w as undetected in the sera and was significantly reduced in the superna tants of actively infected patients, returning to the normal level aft er 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 patie nts had markedly reduced levels of memory T cells (CD3(+)/CD45RO(+)) c ompared with healthy controls. These cells returned to the normal leve ls following successful chemotherapy, T cells are strongly activated i n 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 monocyt es (CD 14(+)) during the acute phase of the disease, but it returned t o the normal range after clinical recovery. These findings therefore s uggest that in Sicilian patients with active VL the cytokine profile i s not clearly characterized by Th2 phenotype as in mice, and both Th1- like and Th2-like cells appear to proliferate and to be activated. Fur thermore, IL-10, rather than IL-4, could play an important part in the inhibition of IFN-gamma-induced macrophage activation and could refle ct the levels of HLA-DR antigen expressed by the monocytes. (C) 1995 A cademic Press Limited.