TY - JOUR KW - Cytokines KW - Dose-Response Relationship, Drug KW - Humans KW - Interferon-gamma KW - Interleukin-12 KW - Interleukin-18 KW - Killer Cells, Natural KW - leprosy KW - Monocytes KW - T-Lymphocytes KW - Tuberculosis, Pulmonary AU - GarcĂ­a V E AU - Uyemura K AU - Sieling P A AU - Ochoa M T AU - Morita C T AU - Okamura H AU - Kurimoto M AU - Rea T H AU - Modlin R L AB -

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.

BT - Journal of immunology (Baltimore, Md. : 1950) C1 - http://www.ncbi.nlm.nih.gov/pubmed/10229854?dopt=Abstract DA - 1999 May 15 IS - 10 J2 - J. Immunol. LA - eng N2 -

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.

PY - 1999 SP - 6114 EP - 21 T2 - Journal of immunology (Baltimore, Md. : 1950) TI - IL-18 promotes type 1 cytokine production from NK cells and T cells in human intracellular infection. UR - http://www.jimmunol.org/content/162/10/6114.full.pdf+html VL - 162 SN - 0022-1767 ER -