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

Visceral leishmaniasis (VL) is characterized by the absence of cytokines su ch as IFN-gamma and IL-12, Cure of VL is associated with a restoration of t he ability to make these cytokines, The aim of the present study was to eva luate the role of IL-12 in the recovery of the ability to produce IFN-gamma and to test whether or not IL-4 IL-10 and/or TGF-beta could suppress IFN-g amma production by PBMC from treated VL patients. High stimulation index (S I) of proliferation was observed in PBMC from subjects stimulated with Leis hmania chagasi antigen (181 +/- 83), Neutralizing IL-12 inhibited lymphopro liferation [stimulation index (SI) of 210 +/- 114 to 1 +/- 0.6 (P<0.01)] an d/or the production of IFN-gamma [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-beta had no effect on this response (147 +/- 22 and 194 +/- 12 respectively), IFN-gamma was high when PBMCs mere stimula ted with L. chagasi (873 +/- 400 pg/ml) and this was abrogated by the addit ion of IL-10 (5 +/- 2 pg/ml), In contrast neither IL-4 or TGF-beta suppress ed IFN-gamma production (837 +/- 244 pg/ml and 759 +/- 523 pg/ml), These re sults indicate that IL-12 plays an important role in the ability of treated VL patients to make IFN-g and that IL-10 but not IL-4 or TGF-beta inhibits this response. (C) 2000 Academic Press.