IL-18 Promotes Type 1 Cytokine Production from NK Cells and T Cells in Human Intracellular Infection

• Published in: The Journal of immunology (1950) Vol. 162; no. 10; pp. 6114 - 6121
• Main Authors: Garcia, Veronica E, Uyemura, Koichi, Sieling, Peter A, Ochoa, Maria T, Morita, Craig T, Okamura, Haruki, Kurimoto, Masashi, Rea, Thomas H, Modlin, Robert L
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.05.1999
• Subjects: Cytokines - biosynthesis; Dose-Response Relationship, Drug; Humans; Interferon-gamma - biosynthesis; Interleukin-12 - immunology; Interleukin-18 - pharmacology; Killer Cells, Natural - drug effects; Leprosy - immunology; Leprosy - pathology; Monocytes - immunology; Mycobacterium leprae; T-Lymphocytes - drug effects; Tuberculosis, Pulmonary - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.10.6114

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.