Overactivation of the immune system by translocated bacteria and bacterial products

T. Hartung, A. Sauer, C. Hermann, F. Brockhaus, A. Wendel

Research output: Contribution to journalShort survey

Abstract

Gut-derived bacteria and their constituents, namely endotoxins, contribute to the pathogenesis of septic multi-organ failure. Ischemia, trauma, chronic inflammation, immunosuppression or reduced blood flow in the gut are conditions that enhance bacterial translocation, which in turn activates the non-specific immune system, i.e. macrophages and granulocytes to release mediators of inflammation such as cytokines, eicosanoids and degranulation products. Besides blood leukocytes, the liver macrophage population (Kupffer cells), the majority of macrophages in the organism, is a central part of the defense. When overactivated this system can turn against the host, resulting in inflammatory organ damage such as liver injury. A variety of cell and animal models was used to characterize the response of blood and liver leukocytes stimulated by bacteria and bacterial wall preparations. Inflammatory hepatocytotoxicity was studied in vivo as well as in a coculture model of Kupffer cells and hepatocytes. A combination of tumor necrosis factor-mediated apoptosis and interleukin-1-mediated necrosis was identified as a crucial mechanism of endotoxin-inducible hepatocytotoxicity in vitro. Lactulose is believed to reduce bacterial translocation and could thus limit the adverse overactivation of the non-specific immune system. In addition, lactulose at high concentrations inhibited Kupffer cell release of inflammatory mediators and protected hepatocytes against macrophage toxicity. The clinical significance of this observation deserves further investigation.

Original languageEnglish (US)
Pages (from-to)98-99
Number of pages2
JournalScandinavian Journal of Gastroenterology, Supplement
Volume32
Issue number222
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

Keywords

  • cytokines
  • endotoxin
  • hepatocytes
  • leukocytes
  • liver injury

ASJC Scopus subject areas

  • Gastroenterology

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