Superantigen and endotoxin synergize in the induction of lethal shock

  • Blank C
  • Luz A
  • Bendigs S
 et al. 
  • 12

    Readers

    Mendeley users who have this article in their library.
  • 81

    Citations

    Citations of this article.

Abstract

Endotoxin (lipopolysaccharide; LPS) and superantigens (exotoxins) have been identified as potent inducers of lethal shock. While endotoxin primarily interacts with CD14 receptors on macrophages, superantigens like the staphylococcal enterotoxin B (SEB) preferentially activate T cells. Both cell types are triggered to release pro-inflammatory cytokines that in turn induce lethal shock. We analyzed whether endotoxin and superantigen interact during the induction phase of lethal shock. We report that LPS and SEB operate synergistically. Lethal doses of both inducers were reduced 100-fold when given in combination. The induced serum levels of tumor necrosis factor, interleukin-6, and interferon-gamma (IFN-gamma) were elevated and remained high for a prolonged period. Moreover, synergistic action of LPS and SEB induced lethal toxic shock even without presensitization of mice with D-galactosamine (D-GalN). Opposed to D-GalN-pretreated mice, mice injected with LPS and SEB showed less liver damage, but rather apoptosis of epithelial cells in the bowel. Cyclosporin A and treatment with anti-IFN-gamma monoclonal antibody blocked the synergistic action of LPS and SEB, indicating that T cell-derived IFN-gamma is the mediator of the observed synergism. Concomitant injection of LPS and SEB had no influence on SEB-induced T cell deletion and anergy induction. Since Gram-positive and Gram-negative bacteria can be recovered from septic blood samples, the synergistic action of endotoxin and superantigens might be relevant during lethal septicemia.

Author-supplied keywords

  • Endotoxin
  • Lethal shock
  • Lipopolysaccharide
  • Staphylococcal enterotoxin B
  • Superantigen

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Christian Blank

  • Arne Luz

  • Sylvia Bendigs

  • Andreas Erdmann

  • Hermann Wagner

  • Klaus Heeg

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free