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Rapamycin Protects Mice from Staphylococcal Enterotoxin B-Induced Toxic Shock and Blocks Cytokine Release In Vitro and In Vivo

  1. Author:
    Krakauer, T.
    Buckley, M.
    Issaq, H. J.
    Fox, S. D.
  2. Author Address

    [Krakauer, Teresa; Buckley, Marilyn] USA, Med Res Inst Infect Dis, Dept Immunol, Integrated Toxicol Div, Frederick, MD 21702 USA. [Issaq, Haleem J.; Fox, Stephen D.] Sci Applicat Int Corp Frederick Inc, Lab Prote & Analyt Technol, Frederick, MD 21702 USA.;Krakauer, T, USA, Med Res Inst Infect Dis, Dept Immunol, Integrated Toxicol Div, Bldg 1425, Frederick, MD 21702 USA.;teresa.krakauer@amedd.army.mil
    1. Year: 2010
    2. Date: Mar
  1. Journal: Antimicrobial Agents and Chemotherapy
    1. 54
    2. 3
    3. Pages: 1125-1131
  2. Type of Article: Article
  3. ISSN: 0066-4804
  1. Abstract:

    Staphylococcal enterotoxins are potent activators for human T cells and cause lethal toxic shock. Rapamycin, an immunosuppressant, was tested for its ability to inhibit staphylococcal enterotoxin B (SEB)-induced activation of human peripheral blood mononuclear cells (PBMC) in vitro and toxin-mediated shock in mice. Stimulation of PMBC by SEB was effectively blocked by rapamycin as evidenced by the inhibition of tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), IL-6, IL-2, gamma interferon (IFN-gamma), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1 alpha (MIP-1 alpha), MIP-1 beta, and T-cell proliferation. In vivo, rapamycin protected 100% of mice from lethal shock, even when administered 24 h after intranasal SEB challenge. The serum levels of MCP-1 and IL-6, after intranasal exposure to SEB, were significantly reduced in mice given rapamycin versus controls. Additionally, rapamycin diminished the weight loss and temperature fluctuations elicited by SEB.

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External Sources

  1. DOI: 10.1128/aac.01015-09
  2. WOS: 000274733300021

Library Notes

  1. Fiscal Year: FY2009-2010
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