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Both cell types are triggered to release pro\u2010inflammatory 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\u2010fold when given in combination. The induced serum levels of tumor necrosis factor, interleukin\u20106, and interferon\u2010\u03b3 (IFN\u2010\u03b3) 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 <jats:sc>D<\/jats:sc>\u2010galactosamine (<jats:sc>D<\/jats:sc>\u2010GalN). Opposed to <jats:sc>D<\/jats:sc>\u2010GalN\u2010pretreated 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\u2010IFN\u2010\u03b3 monoclonal antibody blocked the synergistic action of LPS and SEB, indicating that T cell\u2010derived IFN\u2010\u03b3 is the mediator of the observed synergism. Concomitant injection of LPS and SEB had no influence on SEB\u2010induced T cell deletion and anergy induction. Since Gram\u2010positive and Gram\u2010negative bacteria can be recovered from septic blood samples, the synergistic action of endotoxin and superantigens might be relevant during lethal septicemia.<\/jats:p>","DOI":"10.1002\/eji.1830270405","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T04:32:40Z","timestamp":1172809960000},"page":"825-833","source":"Crossref","is-referenced-by-count":93,"title":["Superantigen and endotoxin synergize in the induction of lethal shock"],"prefix":"10.1002","volume":"27","author":[{"given":"Christian","family":"Blank","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Luz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Bendigs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Erdmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Heeg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,12,6]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.3109\/08830189009056632"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/scientificamerican0892-54"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)91452-Z"},{"key":"e_1_2_1_5_2","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.4049\/jimmunol.148.6.1890","volume":"148","author":"Zanetti G.","year":"1992","journal-title":"J. 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