IL-18 promotes type 1 cytokine production from NK cells and T cells in human intracellular infection.
We investigated the role of IL-18 in leprosy, a disease characterized by polar cytokine responses that correlate with clinical disease. In vivo, IL-18 mRNA expression was higher in lesions from resistant tuberculoid as compared with susceptible lepromatous patients, and, in vitro, monocytes produced IL-18 in response to Mycobacterium leprae. rIL-18 augmented M. leprae-induced IFN-gamma in tuberculoid patients, but not lepromatous patients, while IL-4 production was not induced by IL-18. Anti-IL-12 partially inhibited M. leprae-induced release of IFN-gamma in the presence of IL-18, suggesting a combined effect of IL-12 and IL-18 in promoting M. leprae-specific type 1 responses. IL-18 enhanced M. leprae-induced IFN-gamma production rapidly (24 h) by NK cells and in a more sustained manner (5 days) by T cells. Finally, IL-18 directly induced IFN-gamma production from mycobacteria-reactive T cell clones. These results suggest that IL-18 induces type 1 cytokine responses in the host defense against intracellular infection.
García
V E
VE
Division of Dermatology and Department of Microbiology and Immunology, University of California, Los Angeles, CA 90095, USA.
Uyemura
K
K
Sieling
P A
PA
Ochoa
M T
MT
Morita
C T
CT
Okamura
H
H
Kurimoto
M
M
Rea
T H
TH
Modlin
R L
RL
D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000276:immunology; D020382:Interleukin-18 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects*; D007918:Leprosy / Q000276:immunology* / Q000473:pathology; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects*; D014397:Tuberculosis, Pulmonary / Q000276:immunology
D016207:Cytokines; D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma