IL-10 and IL-12 are the main regulatory cytokines in visceral leishmaniasis

Abstract

Visceral leishmaniasis (VL) is characterized by the absence of cytokines such as IFN-γ and IL-12. Cure of VL is associated with a restoration of the ability to make these cytokines. The aim of the present study was to evaluate the role of IL-12 in the recovery of the ability to produce IFN-γ and to test whether or not IL-4 IL-10 and/or TGF-β could suppress IFN-γ production by PBMC from treated VL patients. High stimulation index (SI) of proliferation was observed in PBMC from subjects stimulated with Leishmania chagasi antigen (181±83). Neutralizing IL-12 inhibited lymphoproliferation [stimulation index (SI) of 210±114 to 1±0.6 (P<0.01)] and/or the production of IFN-γ [2792±402 pg/ml to 407±449 pg/ml (P<0.01)]. Recombinant IL-10 abrogated the lymphoproliferation (SI=2±3) while recombinant IL-4 or TGF-β had no effect on this response (147±22 and 194±12 respectively). IFN-γ was high when PBMCs were stimulated with L. chagasi (873±400 pg/ml) and this was abrogated by the addition of IL-10 (5±2 pg/ml). In contrast neither IL-4 or TGF-β suppressed IFN-γ production (837±244 pg/ml and 759±523 pg/ml). These results indicate that IL-12 plays an important role in the ability of treated VL patients to make IFN-γ and that IL-10 but not IL-4 or TGF-β inhibits this response.