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  • Title: Recovery of IFN-gamma levels in PBMCs from lepromatous leprosy patients through the synergistic actions of the cytokines IL-12 and IL-18.
    Author: Lopez Roa RI, Guerrero Velásquez C, Alvarado Navarro A, Montoya Buelna M, Garcia Niebla C, Fafutis Morris M.
    Journal: Int Immunopharmacol; 2008 Dec 20; 8(13-14):1715-20. PubMed ID: 18708162.
    Abstract:
    The shift to the production of a Th1 cytokine profile during an intracellular infection has been shown to depend on antigen presenting cells-derived IL-12 and T-cell-derived IFN-gamma production. IL-18 facilitates Th1 priming in synergy with IL-12 through the stimulation of IFN-gamma production by T cells, B cells, NK cells, macrophages and DCs. A low level of IFN-gamma production in PBMC cultures from lepromatous leprosy patients (LL) has been previously reported by several groups. We evaluated the synthesis of this cytokine after exogenous addition of recombinant IL-12 and IL-18 (IL12/IL18) in order to induce recovery of the IFN-gamma levels with Mycobacterium leprae antigenic stimulation. The aim of this study was to investigate if exogenous addition of IL12/IL18 to PBMC cell cultures in the presence of M. leprae antigens could induce recovery of IFN-gamma levels. We found that IFN-gamma levels in PBMCs cultured from LL patients were reestablished after exogenous addition of exogenous IL12/IL18 and we also observed a diminished IL-18R expression. Although the molecular mechanisms of IL12/IL18 synergy have not been clearly elucidated, we assume that recombinant cytokines can activate several transcription factors that induce IFN-gamma synthesis.
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