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01 September 2005

Chemotherapeutics targeting immune activation by staphylococcal superantigens.

Teresa Krakauer

Med Sci Monit 2005; 11(9): RA290-295 :: ID: 428464

Abstract

Staphylococcal enterotoxin B (SEB) and related superantigenic toxins arepotent activators of the immune system and cause a variety of diseases in humans, ranging from food poisoningto toxic shock. These toxins bind to both MHC class II molecules and specific Vb regions of T cell receptors(TCR), resulting in the activation of both monocytes/macrophages and T lymphocytes. The interactionsof these toxins with host cells lead to excessive production of proinflammatory cytokines and T cellproliferation, causing clinical symptoms that include fever, hypotension and shock. Different domainsof SEB contributing to MHC class II or TCR interactions have been mapped and defined by mutagenesis,crystallography and other biochemical techniques. This review summarizes the in vitro and in vivo effectsof staphylococcal superantigens, and the therapeutic agents to mitigate their toxic effects. Potentialtargets to prevent the toxic effects of bacterial superantigens include blocking the interaction of SEswith MHC or TCR, or other costimulatory molecules; inhibition of signal transduction pathways used bythese superantigens; inhibition of cytokine and chemokine production; and inhibition of the downstreamsignaling pathways used by proinflammatory cytokines and chemokines. Early blockade of these targetsproves to be useful in vitro and in vivo testing of therapeutics against SEB-induced toxic shock willalso be reviewed.

Keywords: Enterotoxins - toxicity, Immunosuppressive Agents - therapeutic use, Lymphocyte Activation - drug effects, Shock, Septic - immunology, Signal Transduction, Superantigens - toxicity, T-Lymphocytes - immunology

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750