Recovery of IFN-gamma levels in PBMCs from lepromatous leprosy patients through the synergistic actions of the cytokines IL-12 and IL-18.
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.
Lopez Roa
Rocio Ivette
RI
Centro de Investigación en Inmunologia y Dermatología, Instituto Dermatológico de Jalisco, Departamento de Fisiología, CUCS, Universidad de Guadalajara, Mexico.
Guerrero Velásquez
Celia
C
Alvarado Navarro
Anabell
A
Montoya Buelna
Margarita
M
Garcia Niebla
Cesar
C
Fafutis Morris
Mary
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects*; D018664:Interleukin-12 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D053727:Interleukin-18 Receptor alpha Subunit / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D015440:Leprosy, Lepromatous / Q000276:immunology* / Q000382:microbiology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D009166:Mycobacterium leprae / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D000099192:CD69 Antigens
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007371:Interferon-gamma; D018664:Interleukin-12; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D037181:Lectins, C-Type; D008934:Mitogens; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D000099192:CD69 Antigens; C508572:IL18R1 protein, human