Endotoxin-induced serum factor that stimulates gamma interferon production

Abstract

Serum from Mycobacterium bovis BCG-infected mice that had been challenged with lipopolysaccharide (LPS) exhibited a marked ability to induce gamma interferon (IFN-y) in cultures of spleen cells of normal mice in the presence of interleukin-2 (IL-2). The inducing activity became detectable in the circulatory system about 90 min after LPS challenge, disappeared at around 5 h, and was observable upon 640x dilution of the serum. Addition of monoclonal anti-IL-2 receptor antibody to the culture inhibited the induction by the serum. The activity induced high levels of IFN-y even in nylon wool-nonadherent cells, while concanavalin A failed to do so. Serum from uninfected mice challenged with LPS contained no such activity. The molecular weight of the active substance, estimated by gel filtration, was about 70,000. There were pronounced differences among mouse strains in the activities of the sera prepared, which paralleled the amounts of IFN-y produced in vivo. However, the levels of IFN-y produced in whole spleen cells and in nylon wool-nonadherent cells from mice of various strains were the same when stimulated with competent serum. These results indicate the existence of an unidentified factor that induces IFN-y in cooperation with IL-2 in macrophage-depleted splenocytes. They also suggest that IFN-,y production in vivo is not genetically controlled at the lymphocyte level but, rather, at the level of synthesis of the unknown factor.

Interleukin-18 regulates pathological intraocular neovascularization

“…In addition, several other possible mechanisms by which IL-18 regulates ocular angiogenesis could be considered. IL-18 was first described as IGIF [3][4][5], and IFN-␥ and its related cytokines are known to regulate angiogenesis [11,41]. However, we have shown that IFN-␥ and the IFN-␥-related angiostatic cytokines IP-10 and MIG did not increase during the OIR recovery phase (Fig.…”

“…Recently, IL-18, which was first described as an IFN-␥inducing factor (IGIF), has been recognized as a new proinflammatory cytokine [3][4][5]. It is a pleiotropic cytokine produced by activated monocytes, glial cells, and dendritic cells [6], and its immunoregulatory activities include inducing IFN-␥ production [7], enhancing NK cell activity, and promoting the proliferation of activated T cells [5].…”

Overview of interleukin-18: more than an interferon-γ inducing factor

“…In 1989, an endotoxin-induced serum activity that induced IFN-␥ from mouse spleen cells was described by Nakamura and co-workers [1]. This serum activity functioned not as a direct inducer of IFN-␥ but rather as a co-stimulant together with IL-2 or mitogens.…”

“…Interleukin-18 (IL-18), a new pro-inflammatory cytokine IL-18 was first described in 1989 as interferon-␥ (IFN-␥) inducing factor (IGIF) [1]. However, the ability of IL-18 to induce IFN-␥ production is primarily in the context of a second stimulus in that it acts with IL-12, mitogens, or microbial agents to augment IFN-␥ production [2][3][4].…”

Interleukin-18/interferon-γ-inducing factor, a novel cytokine, up-regulates ICAM-1 (CD54) expression in KG-1 cells

“…It has recently been reported that mice injected with heat-killed Propionibacterium acnes released significantly higher levels of interferon-␥ (IFN-␥) into the circulation on challenge with T cell mitogens than mice challenged with T cell mitogens alone [1][2][3][4]. This IFN-␥ production was also induced in vivo when using lipopolysaccharide (LPS) as a mitogen instead of T cell mitogens [5][6][7]. Because it was unlikely that LPS stimulated the T cells directly, some intermediate molecules were considered to be involved.…”