Micallef M J, Ohtsuki T, Kohno K, Tanabe F, Ushio S, Namba M, Tanimoto T, Torigoe K, Fujii M, Ikeda M, Fukuda S, Kurimoto M
Fujisaki Institute, Hayashibara Biochemical Laboratories Inc., Okayama, Japan.
Eur J Immunol. 1996 Jul;26(7):1647-51. doi: 10.1002/eji.1830260736.
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.
新型细胞因子γ干扰素诱导因子（IGIF）可增强人外周血单个核细胞（PBMC）培养物中的自然杀伤（NK）细胞活性，这与结构不相关的细胞因子白细胞介素（IL）-12类似。已发现IGIF可增强γ干扰素（IFN-γ）和粒细胞/巨噬细胞集落刺激因子（GM-CSF）的产生，同时抑制伴刀豆球蛋白A（Con A）刺激的PBMC中IL-10的产生。在本研究中，当抗CD3单克隆抗体（mAb）刺激的人富集T细胞暴露于IGIF时，该细胞因子剂量依赖性地增强细胞增殖，并且在较低浓度的IGIF下，这可被抗IL-2中和抗体完全抑制。在较高浓度的IGIF下，抗IFN-γ中和抗体对T细胞增殖仅有微不足道的抑制作用。酶联免疫吸附测定（ELISA）显示，与PBMC一样，暴露于IGIF的T细胞产生大量的IFN-γ；然而，IL-4和IL-10产生的变化很小。分别通过CTLL-2生物测定和ELISA确定，IGIF而非IL-12显著增强T细胞培养物中IL-2和GM-CSF的产生；然而，IGIF和IL-12均增强T细胞产生IFN-γ。当T细胞暴露于IGIF和IL-12的组合时，观察到对IFN-γ产生有协同作用，但对IL-2和GM-CSF产生没有协同作用。总之，IGIF显然通过IL-2依赖性途径增强T细胞增殖，并在体外增强Th1细胞因子产生，并且在增强IFN-γ产生方面与IL-12联合时表现出协同作用，但在增强IL-2和GM-CSF产生方面没有协同作用。基于与任何已知细胞因子的结构和功能差异，最近有人提议将该细胞因子命名为白细胞介素-18。
