intranasal rapamycin rescues mice from staphylococcal enterotoxin b-induced shock鼻内雷帕霉素救老鼠从葡萄球菌肠毒素b-induced冲击.pdfVIP

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intranasal rapamycin rescues mice from staphylococcal enterotoxin b-induced shock鼻内雷帕霉素救老鼠从葡萄球菌肠毒素b-induced冲击.pdf

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intranasal rapamycin rescues mice from staphylococcal enterotoxin b-induced shock鼻内雷帕霉素救老鼠从葡萄球菌肠毒素b-induced冲击

Toxins 2012, 4, 718-728; doi:10.3390/toxins4090718 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Brief Report Intranasal Rapamycin Rescues Mice from Staphylococcal Enterotoxin B-Induced Shock Teresa Krakauer * and Marilyn Buckley Integrated Toxicology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA; E-Mail: marilyn.buckley@ * Author to whom correspondence should be addressed; E-Mail: Teresa.krakauer@; Tel.: +1-301-619-4733. Received: 2 July 2012; in revised form: 6 August 2012 / Accepted: 13 August 2012 / Published: 18 September 2012 Abstract: Staphylococcal enterotoxin B (SEB) and related exotoxins produced by Staphylococcus aureus are potent activators of the immune system and cause toxic shock in humans. Currently there is no effective treatment except for the use of intravenous immunoglobulins administered shortly after SEB exposure. Intranasal SEB induces long-lasting lung injury which requires prolonged drug treatment. We investigated the effects of rapamycin, an immunosuppressive drug used to prevent graft rejection, by intranasal administration in a lethal mouse model of SEB-induced shock. The results show that intranasal rapamycin alone delivered as late as 17 h after SEB protected 100% of mice from lethal shock. Additionally, rapamycin diminished the weight loss and temperature fluctuations elicited by SEB. Intranasal rapam