Hepatic injury and lethal shock in galactosamine-sensitized mice induced by the superantigen staphylococcal enterotoxin B

Autor: Hiroo Ohnishi, Tetsuya Yamada, Kimiyasu Sano, Yasutoshi Muto, Tomoo Naito, Hisataka Moriwaki, Masahito Nagaki, Shigeo Yasuda, Teruo Maeda
Rok vydání: 1994
Předmět:
Zdroj: Gastroenterology. 106:450-458
ISSN: 0016-5085
DOI: 10.1016/0016-5085(94)90604-1
Popis: 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. Methods: 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. Results: Intraperitoneal administration of SEB (50 μg) caused lethal shock (50% mortality) associated with massive hepatic necrosis in GaIN-sensitized mice, with no mortality on injection of up to 100 μg SEB alone. Within 2 hours after injection of SEB, serum tumor necrosis factor α (TNF-α) levels reached a peak, followed by high levels of serum interferon-γ (IFN-γ) up to 10 hours after injection. Passive immunization with anti-TNF-α/β-neutralizing monoclonal antibody (mAb) protected GaIN-sensitized mice from the lethal effects of SEB, with less protection with anti-IFN-γ-neutralizing mAb. SEB induced the production of TNF-α and IFN-γ in a dose-dependent manner from splenic mononuclear cells in vitro. Conclusions: The results show that SEB contributes to lethal shock associated with severe hepatic injury in GaIN-sensitized mice and suggest that TNF-α and IFN-γ produced in response to SEB may be mediators of the lethal toxicity and hepatotoxicity of SEB.
Databáze: OpenAIRE