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IL-10 and IL-12 are the main regulatory cytokines in visceral leishmaniasis |
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| Authors: | Bacellar O D'oliveira A Jerônimo S Carvalho E M |
| Institution: | 1. Laboratory of Cellular Immunology, Area of Pathology, Faculty of Medicine, University of Brasilia, Brasilia, Distrito Federal, Brazil;2. Laboratory of Cellular and Molecular Immunology, René Rachou Research Center, Belo Horizonte, Minas Gerais, Brazil;3. Laboratory of Immunology and Inflammation, Department of Cell Biology, Institute of Biology, University of Brasilia, Brasilia, Distrito Federal, Brazil;1. Interdisciplinary Program in Genetics, University of Iowa, Iowa City, IA, USA;2. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA;3. Department of Infectious Diseases, Federal University of Rio Grande do Norte, Natal, RN, Brazil;4. Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, RN, Brazil;5. Cambridge Institute for Medical Research, University of Cambridge, UK;6. Telethon Kids Institute, The University of Western Australia, Perth, Australia;7. Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, RN, Brazil;8. Institute of Science and Technology of Tropical Diseases, Brazil;9. Department of Internal Medicine, University of Iowa, Iowa City, IA, USA;10. Department of Microbiology, University of Iowa, Iowa City, IA, USA;11. Iowa City Veterans'' Affairs Medical Center, Iowa City, IA, USA |
| Abstract: | 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. |
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