Chapter 15 : Small Nonpeptide Inhibitors of Staphylococcal Superantigen-Induced Cytokine Production and Toxic Shock

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Staphylococcal superantigens are grouped into three classes based on their primary sequence homology. In humans and monkeys, Staphylococcal enterotoxins (SEs) induce an emetic response and toxic shock at submicrogram concentrations. The mouse models commonly used today rely on the use of sensitizing agents such as D-galactosamine, actinomycin D, lipopolysaccharide (LPS), or viruses to induce toxic shock. None of the existing mouse models faithfully reproduces all of the complex events of human toxic shock syndrome. Bacterial superantigens cause toxic shock and contribute to septic complications during infection. Staphylococcal toxic shock syndrome (TSS) is characterized by fever, hypotension, desquamation of skin, fever, and dysfunction of three or more organ systems. Superantigens from both and are the causative agents of staphylococcal and streptococcal toxic shock. Given the complex pathophysiology of toxic shock, an understanding of the interaction of cellular receptors and signaling pathways used by these staphylococcal superantigens and the biological mediators they induce provides invaluable insight into selecting appropriate therapeutic targets. A list of small nonpeptide inhibitors effective in blocking the effects of superantigens is shown in this chapter. The anti-inflammatory cytokine interleukin 10 (IL-10) was used to block the production of IL-1, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ), resulting in reduced lethality to superantigen-induced toxic shock. The ability to stop the inflammatory events initiated by superantigens early appears to be critical in preventing toxic shock.

Citation: Krakauer T. 2007. Small Nonpeptide Inhibitors of Staphylococcal Superantigen-Induced Cytokine Production and Toxic Shock, p 229-244. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch15
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Figure 1.

Cells and mediators participating in superantigen-induced toxic shock.

Citation: Krakauer T. 2007. Small Nonpeptide Inhibitors of Staphylococcal Superantigen-Induced Cytokine Production and Toxic Shock, p 229-244. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch15
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Generic image for table
Table 1.

Small nonpeptide therapeutics for SEB-induced shock

Citation: Krakauer T. 2007. Small Nonpeptide Inhibitors of Staphylococcal Superantigen-Induced Cytokine Production and Toxic Shock, p 229-244. In Kotb M, Fraser J (ed), Superantigens. ASM Press, Washington, DC. doi: 10.1128/9781555815844.ch15

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