02029nas a2200373   4500000000100000008004100001260001600042653001400058653003700072653001100109653002100120653001900141653001900160653002600179653001200205653001400217653001800231653002800249100001600277700001400293700001600307700001400323700001500337700001400352700001500366700001200381700001500393245010600408856006200514300001200576490000800588520104500596022001401641       1999                            d  c1999 May 1510aCytokines10aDose-Response Relationship, Drug10aHumans10aInterferon-gamma10aInterleukin-1210aInterleukin-1810aKiller Cells, Natural10aleprosy10aMonocytes10aT-Lymphocytes10aTuberculosis, Pulmonary1 aGarcía V E1 aUyemura K1 aSieling P A1 aOchoa M T1 aMorita C T1 aOkamura H1 aKurimoto M1 aRea T H1 aModlin R L00aIL-18 promotes type 1 cytokine production from NK cells and T cells in human intracellular infection.  uhttp://www.jimmunol.org/content/162/10/6114.full.pdf+html  a6114-210 v1623 a<p>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.</p>  a0022-1767