title: Interferon-gamma-inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon-gamma production.
abstract: The novel cytokine interferon-gamma-inducing factor (IGIF) augments natural killer (NK) cell activity in cultures of human peripheral blood mononuclear cells (PBMC), similarly to the structurally unrelated cytokine interleukin (IL)-12. IGIF has been found to enhance the production of interferon-gamma (IFN-gamma) and granulocyte/macrophage colony-stimulating factor (GM-CSF) while inhibiting the production of IL-10 in concanavalin A (Con A)-stimulated PBMC. In this study, when anti-CD3 monoclonal antibody (mAb)-stimulated human enriched T cells were exposed to IGIF, the cytokine dose-dependently enhanced the proliferation of the cells and this could be completely inhibited by a neutralizing antibody against IL-2 at lower concentrations of IGIF. Neutralizing antibody against IFN-gamma had only insignificant inhibitory effects on T cell proliferation at higher concentrations of IGIF. Enzyme-linked immunosorbent assays (ELISA) revealed that, like PBMC, T cells exposed to IGIF produced large amounts of IFN-gamma; however, changes in the production of IL-4 and IL-10 were minimal. IGIF, but not IL-12, significantly enhanced IL-2 and GM-CSF production in T cell cultures, as determined by CTLL-2 bioassay and ELISA, respectively; however, both IGIF and IL-12 enhanced IFN-gamma production by the T cells. When T cells were exposed to a combination of IGIF and IL-12, a synergistic effect was observed on the production of IFN-gamma, but not on production of IL-2 and GM-CSF. In conclusion, IGIF enhances T cell proliferation apparently through an IL-2-dependent pathway and enhances Th1 cytokine production in vitro and exhibits synergism when combined with IL-12 in terms of enhanced IFN-gamma production but not IL-2 and GM-CSF production. Based on structural and functional differences from any known cytokines, it was recently proposed that this cytokine be designated interleukin-18.
authors.affiliation: Fujisaki Institute, Hayashibara Biochemical Laboratories Inc., Okayama, Japan.
authors.forename: M J
authors.initials: MJ
authors.lastname: Micallef
authors.forename: T
authors.initials: T
authors.lastname: Ohtsuki
authors.forename: K
authors.initials: K
authors.lastname: Kohno
authors.forename: F
authors.initials: F
authors.lastname: Tanabe
authors.forename: S
authors.initials: S
authors.lastname: Ushio
authors.forename: M
authors.initials: M
authors.lastname: Namba
authors.forename: T
authors.initials: T
authors.lastname: Tanimoto
authors.forename: K
authors.initials: K
authors.lastname: Torigoe
authors.forename: M
authors.initials: M
authors.lastname: Fujii
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: S
authors.initials: S
authors.lastname: Fukuda
authors.forename: M
authors.initials: M
authors.lastname: Kurimoto
mesh_terms: D000328:Adult; D016207:Cytokines / Q000096:biosynthesis* / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000494:pharmacology*; D020382:Interleukin-18; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D020382:Interleukin-18; D007376:Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma