The effect of cyclosporin A in murine visceral leishmaniasis

Leishmania donovani is an obligate intracellular protozoan parasite of macrophages whose control is effected by cellular mechanism. In order to determine the role of T-helper cells and their soluble mediators in the control of the infection, the effects of cyclosporin A (CsA) were studied in strains of mice (C57L/J and C57BL/6J) known to be resistant and susceptible. Mice treated with CsA (200 mg/kg) exhibited as early as day 15 a significant increase in the level of their infection. The number of parasites was 3 times higher in CsA-treated mice of both strains when compared to untreated controls. The proportional difference in the level of infection between C57BL/6J and C57L/J mice was, however, not affected by treatment. Infection and CsA treatment, respectively, reduced or abolished the capacity of spleen cells to produce IL-2. Infection also abolished the production of IL-1 by macrophages. Both strains were, however, able to recover from the infection without functional T-helper lympho-cytes and/or the IL-1 IL-2 which had been inhibited by treatment with CsA.