Lethal Escherichia coli and Salmonella typhimurium endotoxemia is mediated through different pathways.
SourceEuropean Journal of Immunology, 31, 9, (2001), pp. 2529-2538
Article / Letter to editor
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European Journal of Immunology
SubjectChronic arthritis: Pathogenesis and treatment; The role of cytokines in the pathophysiology of febrile illnesses and in host defense against infections; Development of radiopharmaceuticals for diagnosis and therapy of pathological processes.; Chronische arthritis: Pathogenese en behandeling; De rol van cytokinen in de pathofysiologie van koortsende ziekten en in de afweer tegen infecties; Ontwikkeling van radiofarmaca ten behoeve van diagnose en behandeling van ziekteprocessen.
Despite the differences in the molecular structure between lipopolysaccharides (LPS) isolated from Escherichia coli, Klebsiella pneumoniae or Salmonella typhimurium, the potential differences in their biological effects in vivo have not been investigated. In the present study, TNF and LT double knock-out (TNF-/-LT-/-) mice were almost as susceptible as TNF?? controls to S. typhimurium LPS, but they were significantly more resistant to lethal endotoxemia induced by E. coli or K. pneumoniae LPS. The effect was not due to endotoxin-associated proteins. In the knock-out mice, this difference in lethality was accompanied by decreased interleukin-1 (IL-1) and interferon-gamma (IFN-gamma) production after challenge with E. coli LPS, whereas after S. typhimurium LPS more IL-1 and IFN-gamma were produced. In contrast, more IL-10 was produced after challenge of mice with E. coli LPS than with S. typhimurium LPS. The hypothesis that a combination of pro-inflammatory cytokines is responsible for the mortality after S. typhimurium LPS was suggested by experiments in mice deficient in IL-1beta-converting enzyme (ICE-/- mice). ICE-/-mice, lacking mature IL-1beta and IL-18, but also defective in IFN-gamma and TNF production, were completely protected against both E. coli and S. typhimurium LPS. Experiments in Toll-like receptor (TLR)-4 defective mice suggested that the difference is not due to differential activation of TLR4. In conclusion, TNF and LT play a central role in the lethality due to E. coli LPS, whereas the lethal effects of S. typhimurium LPS are mediated through mechanisms also involving other cytokines such as IFN-gamma, IL-1 and IL-18.
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