Accession Number : ADA565727


Title :   Intranasal Rapamycin Rescues Mice from Staphylococcal Enterotoxin B-Induced Shock


Descriptive Note : Journal article


Corporate Author : ARMY MEDICAL RESEARCH INST OF INFECTIOUS DISEASES FORT DETRICK MD


Personal Author(s) : Krakauer, Teresa ; Buckley, Marilyn


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a565727.pdf


Report Date : 18 Sep 2012


Pagination or Media Count : 12


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 rapamycin attenuated lung MCP-1, IL-2, IL-6, and IFN gama by 70%, 30%, 64%, and 68% respectively. Furthermore, short courses (three doses) of rapamycin were sufficient to block SEB-induced shock. Intranasal rapamycin represents a novel use of an immunosuppressant targeting directly to site of toxin exposure, reducing dosages needed and allowing a wider therapeutic window.


Descriptors :   *ENTEROTOXINS , *SHOCK , *STAPHYLOCOCCUS , *STAPHYLOCOCCUS AUREUS , *TOXICITY , ANATOMICAL MODELS , CHEMOTHERAPY , DOSAGE , DRUGS , EXOTOXINS , IMMUNOGLOBULINS , IMMUNOSUPPRESSION , POTENCY , VEINS , WOUNDS AND INJURIES


Subject Categories : Toxicology
      Microbiology


Distribution Statement : APPROVED FOR PUBLIC RELEASE