title: Intranasal rapamycin rescues mice from staphylococcal enterotoxin B-induced shock.
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 IFNγ 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.
authors.affiliation: Integrated Toxicology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. marilyn.buckley@us.army.mil
authors.forename: Teresa
authors.initials: T
authors.lastname: Krakauer
authors.forename: Marilyn
authors.initials: M
authors.lastname: Buckley
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D004768:Enterotoxins; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012769:Shock / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D020123:Sirolimus / Q000008:administration & dosage*; D013211:Staphylococcus aureus
chemical_list: D016207:Cytokines; D004768:Enterotoxins; D007166:Immunosuppressive Agents; C031818:enterotoxin B, staphylococcal; D020123:Sirolimus
keywords: intranasal rapamycin; shock; staphylococcal enterotoxin B