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


CONCLUSIONS
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.
Nagaki
M
M
First Department of Internal Medicine, Gifu University School of Medicine, Japan.
Muto
Y
Y
Ohnishi
H
H
Yasuda
S
S
Sano
K
K
Naito
T
T
Maeda
T
T
Yamada
T
T
Moriwaki
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D004768:Enterotoxins / Q000633:toxicity*; D005688:Galactosamine; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D012769:Shock / Q000209:etiology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000633:toxicity*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D004768:Enterotoxins; D008070:Lipopolysaccharides; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D005688:Galactosamine