Regulation of interferon-gamma production by IL-12 and IL-18.
IL-18 (interferon-inducing factor) and IL-12 exhibit a marked synergism in interferon-gamma induction in T cells. Investigations into the mechanism of this synergism have revealed that IL-12 upregulates expression of the IL-18 receptor on cells producing interferon-gamma. Although IL-18 does not induce the development of Th1 cells, it is essential for the effective induction and activation of Th1 cells by IL-12. As for natural killer cells, IL-18 seems to activate them independently of IL-12. Although IL-12 and IL-18 activate both innate and acquired immunity, their excessive production by activated macrophages may induce multiple organ disorders including disruption of the immune system.
Okamura
H
H
Laboratory of Host Defenses, Hyogo College of Medicine, Nishinomiya, Japan.
Kashiwamura
S
S
Tsutsui
H
H
Yoshimoto
T
T
Nakanishi
K
K
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology* / Q000502:physiology / Q000633:toxicity; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D018664:Interleukin-12 / Q000494:pharmacology* / Q000502:physiology / Q000633:toxicity; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018448:Models, Immunological; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics; D053724:Receptors, Interleukin-18; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
D016207:Cytokines; C508573:Il18r1 protein, mouse; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma