Nagaki M, Muto Y, Ohnishi H, Yasuda S, Sano K, Naito T, Maeda T, Yamada T, Moriwaki H
First Department of Internal Medicine, Gifu University School of Medicine, Japan.
Gastroenterology. 1994 Feb;106(2):450-8. doi: 10.1016/0016-5085(94)90604-1.
BACKGROUND/AIMS: Staphylococcal enterotoxin B (SEB) acts as a superantigen binding to class II major histocompatibility complex proteins, and this complex stimulates T cells. The aim of this study was to investigate the pathogenic effects of SEB on hepatic injury and lethal shock in mice.
SEB was administered to D-galactosamine (GalN)-sensitized mice, and the degree of liver injury and levels of circulating cytokines were determined. In vitro cytokine production in response to SEB was also investigated.
Intraperitoneal administration of SEB (50 micrograms) caused lethal shock (50% mortality) associated with massive hepatic necrosis in GalN-sensitized mice, with no mortality on injection of up to 100 micrograms SEB alone. Within 2 hours after injection of SEB, serum tumor necrosis factor alpha (TNF-alpha) levels reached a peak, followed by high levels of serum interferon-gamma (IFN-gamma) up to 10 hours after injection. Passive immunization with anti-TNF-alpha/beta-neutralizing monoclonal antibody (mAb) protected GalN-sensitized mice from the lethal effects of SEB, with less protection with anti-IFN-gamma-neutralizing mAb. SEB induced the production of TNF-alpha and IFN-gamma in a dose-dependent manner from splenic mononuclear cells in vitro.
The results show that SEB contributes to lethal shock associated with severe hepatic injury in GalN-sensitized mice and suggest that TNF-alpha and IFN-gamma produced in response to SEB may be mediators of the lethal toxicity and hepatotoxicity of SEB.
背景/目的：葡萄球菌肠毒素B（SEB）作为一种超抗原，可与II类主要组织相容性复合体蛋白结合，该复合体可刺激T细胞。本研究旨在探讨SEB对小鼠肝损伤和致死性休克的致病作用。
将SEB给予D-半乳糖胺（GalN）致敏的小鼠，测定肝损伤程度和循环细胞因子水平。还研究了体外对SEB的细胞因子产生情况。
腹腔注射SEB（50微克）可导致GalN致敏小鼠发生致死性休克（死亡率50%），并伴有大量肝坏死，单独注射高达100微克SEB则无死亡。注射SEB后2小时内，血清肿瘤坏死因子α（TNF-α）水平达到峰值，随后在注射后10小时内血清干扰素-γ（IFN-γ）水平升高。用抗TNF-α/β中和单克隆抗体（mAb）进行被动免疫可保护GalN致敏小鼠免受SEB的致死作用，而用抗IFN-γ中和mAb的保护作用较小。SEB在体外以剂量依赖方式诱导脾单核细胞产生TNF-α和IFN-γ。
结果表明，SEB导致GalN致敏小鼠发生与严重肝损伤相关的致死性休克，并提示对SEB产生的TNF-α和IFN-γ可能是SEB致死毒性和肝毒性的介质。
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