Genetic component in the inflammatory response induced by bacterial lipopolysaccharide

Antonio De Maio, Maria De Lourdes Mooney, Lydia E. Matesic, Charles N. Paidas, Roger H. Reeves

Research output: Contribution to journalArticle

Abstract

Multiple organ dysfunction syndrome (MODS) appears to be the result of a complex program influenced by multiple factors, including environmental, physiological, and immunological conditions. Thus, an uncontrolled inflammatory response following a stochastic event, the initial injury, is believed to be the cause for the development of this syndrome. Several lines of evidence suggest that a genetic component could contribute to the regulation of the inflammatory response, as well, but no direct evidence demonstrates a heritable predisposition to MODS. In the present study, a genetic contribution was demonstrated for the inflammatory response induced by the administration of bacterial lipopolysaccharide (LPS) in different, genetically distinct strains of inbred mice. A survey of five inbred strains showed that mortality following administration of Escherichia coli LPS (20 mg/kg) was highest in C57BL/6J (B6) mice, while A/J mice were the most resistant. Accordingly, B6 and A/J mice were examined further for differences in the inflammatory response elicited by LPS. B6 mice showed higher levels of circulating interleukin-1β and interleukin-6, as well as higher mRNA levels of hepatic β-fibrinogen (an acute-phase gene) and metallothionein. Surprisingly, the circulating levels of tumor necrosis factor-α were significantly higher in A/J than in B6 mice after LPS administration. Since B6 and A/J mice were bred and raised in identical environments and received the same LPS challenge, the contrasting inflammatory response that was observed is largely attributable to genetic differences between these two strains. These data illustrate that the response to injury could be modulated by the genetic background of the individual. This information may be pertinent for the care of critically ill patients.

Original languageEnglish (US)
Pages (from-to)319-323
Number of pages5
JournalShock
Volume10
Issue number5
DOIs
StatePublished - Nov 1998

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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