Document Detail

Superantigen and endotoxin synergize in the induction of lethal shock.
MedLine Citation:
PMID:  9130631     Owner:  NLM     Status:  MEDLINE    
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.
C Blank; A Luz; S Bendigs; A Erdmann; H Wagner; K Heeg
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of immunology     Volume:  27     ISSN:  0014-2980     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-05-22     Completed Date:  1997-05-22     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  825-33     Citation Subset:  IM    
Institute of Medical Microbiology, Immunology and Hygiene, Munich, Germany.
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MeSH Terms
Antibodies, Blocking / pharmacology
Antibodies, Monoclonal / pharmacology
Clonal Anergy
Clonal Deletion
Cyclosporine / pharmacology
Cytokines / biosynthesis,  blood
Drug Synergism
Enterotoxins / administration & dosage,  antagonists & inhibitors,  pharmacology*
Galactosamine / administration & dosage,  analogs & derivatives
Injections, Intravenous
Interferon-gamma / immunology
Lipopolysaccharides / administration & dosage,  antagonists & inhibitors,  pharmacology*
Mice, Inbred BALB C
Receptors, Antigen, T-Cell, alpha-beta / immunology
Shock, Septic / etiology*,  pathology
Staphylococcus aureus / immunology*
Superantigens / administration & dosage,  immunology,  pharmacology*
T-Lymphocyte Subsets / immunology,  metabolism
Reg. No./Substance:
0/Antibodies, Blocking; 0/Antibodies, Monoclonal; 0/Cytokines; 0/Enterotoxins; 0/Lipopolysaccharides; 0/Receptors, Antigen, T-Cell, alpha-beta; 0/Superantigens; 39424-53-8/enterotoxin B, staphylococcal; 59865-13-3/Cyclosporine; 7535-00-4/Galactosamine; 82115-62-6/Interferon-gamma

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