title: IL-12 enhances Th1-type responses in human Leishmania donovani infections.
abstract: IL-12 is a pluripotent cytokine that interacts with NK and T cells to play a central role in the initiation and maintenance of Th1 responses and IFN-gamma production. Because of the interactive relationship between IL-12 and IFN-gamma response to infectious organisms, a study was undertaken to examine the role of IL-12 in the immune regulation of human visceral leishmaniasis (VL). Human (Hu) VL is associated with immune dysfunction and the appearance of IL-10 mRNA, not present in healed individuals. We found that PBMC from treated VL patients produced both IL-12 p40 and IFN-gamma in response to in vitro stimulation with Leishmania donovani. The production of both IL-12 p40 and IFN-gamma were interdependent and were abrogated by the addition of exogenous Hu rIL-10. In contrast, PBMC from active VL patients did not produce IL-12 p40 or IFN-gamma in response to L. donovani lysate. Neutralizing anti-IL-10 mAb led to the enhancement of IFN-gamma production by active VL PBMC cultured with L. donovani lysate, and this enhanced IFN-gamma production was blocked by anti-IL-12 mAb. The addition of exogenous Hu rIL-12 to PBMC from active VL patients resulted in the augmentation of IFN-gamma in response to L. donovani lysate. Therefore, treatment of active VL patient PBMC with anti-IL-10 or IL-12 shifted the response toward a Th1-type response with the production of IFN-gamma. These results indicate that IL-12 may play an important role in the regulation of the cellular immune responses in Hu VL.
authors.affiliation: Department of Microbiology, College of Medicine, University of Juba, Khartoum, Sudan.
authors.forename: H W
authors.initials: HW
authors.lastname: Ghalib
authors.forename: J A
authors.initials: JA
authors.lastname: Whittle
authors.forename: M
authors.initials: M
authors.lastname: Kubin
authors.forename: F A
authors.initials: FA
authors.lastname: Hashim
authors.forename: A M
authors.initials: AM
authors.lastname: el-Hassan
authors.forename: K H
authors.initials: KH
authors.lastname: Grabstein
authors.forename: G
authors.initials: G
authors.lastname: Trinchieri
authors.forename: S G
authors.initials: SG
authors.lastname: Reed
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology*; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma