Endotoxin-inducible cytotoxicity in liver cell cultures-II. Demonstration of endotoxin-tolerance

T. Hartung, A. Wendel

Research output: Contribution to journalArticle

Abstract

Endotoxins from gram negative bacteria, central mediators of septic shock, share the characteristic property of inducing tolerance against their own action. This work investigates whether a corresponding ex-vivo tolerance can be observed in a cellular system with endotoxin-inducible hepatocytoxicity. The following experimental approaches were chosen in order to induce an endotoxinunresponsive state prior to cell preparation: (1) pretreatment of rats with endotoxin, (2) partial hepatectomy, (3) use of neonatal rats and (4) pretreatment of rats with silica. An in-vivo protection against endotoxin-induced liver injury was obtained by all of these four measures: cells prepared from these groups of animals showed greatly diminished sensitivity towards endotoxin-induced hepatocytotoxicity in vitro. The suppressed endotoxin sensitivity after silica pretreatment was partially restored in vitro by the addition of native Kupffer cells (KC). Isolated KC of all but the endotoxin pretreated animals secreted tumor necrosis factor-α in response to endotoxin. It is concluded that different types of tolerance can be distinguished: (a) impairment of macrophage functions (silica pretreatment), (b) hepatocyte unresponsiveness (neonatal rats and hepatectomy) and (c) impaired macrophage function combined with hepatocyte unresponsiveness (endotoxin-pretreated rats).

Original languageEnglish (US)
Pages (from-to)191-196
Number of pages6
JournalBiochemical Pharmacology
Volume43
Issue number2
DOIs
StatePublished - Jan 22 1992
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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