IL-10 and IL-12 are the main regulatory cytokines in visceral leishmaniasis.
Visceral leishmaniasis (VL) is characterized by the absence of cytokines such as IFN-gamma 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-gamma and to test whether or not IL-4 IL-10 and/or TGF-beta could suppress IFN-gamma 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-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 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-beta suppressed IFN-gamma 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-gamma and that IL-10 but not IL-4 or TGF-beta inhibits this response.
Bacellar
O
O
Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos-UFBA, Salvador-Bahia, Brasil.
D'oliveira
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A
Jerônimo
S
S
Carvalho
E M
EM
D000906:Antibodies / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D018664:Interleukin-12 / Q000097:blood* / Q000276:immunology; D015847:Interleukin-4 / Q000097:blood; D007898:Leishmaniasis, Visceral / Q000097:blood* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000097:blood
D000906:Antibodies; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4