title: Interleukin-18 (IL-18) synergizes with IL-2 to enhance cytotoxicity, interferon-gamma production, and expansion of natural killer cells.
abstract: We investigated the in vitro effects of combining interleukin-18 (IL-18) and IL-2 on human lymphocytes. The combined use of these two cytokines synergistically enhanced the proliferation, cytolytic activity, and interferon-gamma production of peripheral blood mononuclear cells. Phenotypic analysis revealed a preferential expansion of CD56+CD3- cells and an up-regulation of IL-2 receptor-alpha expression on natural killer cells. Isolated natural killer cells showed a substantial increase in proliferation and cytotoxicity compared with CD4+ and CD8+ T cells. The combined use of IL-18 and IL-2 should be considered a viable strategy to induce an antitumor response in vivo.
authors.affiliation: Department of Surgery, University of Pittsburgh Cancer Institute, Pennsylvania 15261, USA.
authors.forename: Y I
authors.initials: YI
authors.lastname: Son
authors.forename: R M
authors.initials: RM
authors.lastname: Dallal
authors.forename: R B
authors.initials: RB
authors.lastname: Mailliard
authors.forename: S
authors.initials: S
authors.lastname: Egawa
authors.forename: Z L
authors.initials: ZL
authors.lastname: Jonak
authors.forename: M T
authors.initials: MT
authors.lastname: Lotze
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D020382:Interleukin-18 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D020382:Interleukin-18; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma