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Toxicologic Pathology
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Murine Lethal Toxic Shock Caused by Intranasal Administration of Staphylococcal Enterotoxin B

Vladimir Savransky

Department of Experimental Pathology, Division of Pathology, Department of Bacterial Diseases

Victor Rostapshov

Department of Experimental Pathology, Division of Pathology, Department of Bacterial Diseases

Dmitriy Pinelis

Good Samaritan Hospital, 5601 Loch Raven Boulevard, Baltimore, Maryland 21239

Yury Polotsky

Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910

Sergey Korolev

Department of Experimental Pathology, Division of Pathology, Department of Bacterial Diseases

Jack Komisar

Department of Experimental Pathology, Division of Pathology, Department of Bacterial Diseases

Konstantin Fegeding

Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814, kfegeding{at}USUHS.MIL

Currently available murine staphylococcal enterotoxin B (SEB) shock models require pretreatment with various agents to increase mouse sensitivity to SEB. This study was performed to show that C3H/HeJ mice are highly susceptible to intranasal SEB inoculation, which caused toxic shock without using pretreatment agents. For this purpose, mice were injected intranasally with different doses of SEB and observed for up to 1 month. The median lethal dose of SEB was determined using the probit procedure. Tissue samples were taken at different time points for histopathological examination. The LD50 was found at 1.6 µg/g (95% fiducial limit (f.l.) 0.7 to 2.2), the LD80 at 2.7 µg/g (95% f.l. 1.9 to 4.0) and the LD90 at 3.6 µg/g (95% f.l. 2.7 to 6.4). Histopathologic examination revealed pulmonary edema and bronchopneumonia. Mucosal-associated lymphoid tissue first became activated, followed by increasing lymphocyte apoptosis and depletion. In the liver there were intralobular and portal inflammatory foci with increasing lymphocyte apoptosis and degenerative necrosis. The splenic white pulp was characterized by early activation and subsequent depletion of lymphoid follicle germinal centers. The thymus initially was activated, followed by increasing apoptosis and migration of lymphoid cells from the cortex to the medulla. The pathological features detected in the mice were similar to those of rhesus monkeys treated with SEB aerosol challenge.

Key Words: Staphylococcal enterotoxin B • superantigen • toxic shock • animal model • histopathology • immune system.

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Toxicologic Pathology, Vol. 31, No. 4, 373-378 (2003)
DOI: 10.1080/01926230390201093
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