Genetic background conditions the effect of sex steroids on the inflammatory response during endotoxic shock

Heiko Trentzsch, Dylan Stewart, Antonio De Maio

Research output: Contribution to journalArticle

Abstract

Objective: The contribution of gender to the mortality and morbidity of trauma patients is controversial. In addition, a genetic contribution has been recently indicated. The influence of these two variables was studied in a murine model of endotoxemia. Design: Prospective, controlled, and randomized animal study. Setting: A university research laboratory. Subjects: Female and male mice (6-8 wks old) were injected with Escherichia coli lipopolysaccharide (15 mg/kg). Additionally, mice were gonadectomized and supplemented with 5-α-dihydrotestosterone (357 mg/day), 17-β-estradiol (23.8 μg/day), or placebo for 21 days and injected with lipopolysaccharide. Tumor necrosis factor-α was measured in plasma samples obtained after 1.5 hrs of lipopolysaccharide injection. Measurements and Main Results: Higher tumor necrosis factor-α plasma levels were observed in C57BL/6J (B6) female mice as compared with males. Because this phenotype is not sex linked, we evaluated the role of sex steroids. Castrated male B6 mice showed higher lipopolysaccharide-induced tumor necrosis factor-α plasma levels than nonoperated controls. These lipopolysaccharide-induced tumor necrosis factor-α levels were further increased after the administration of 17-β-estradiol to castrated B6 male mice as compared with nonoperated male or female mice. In addition, 17-β-estradiol-supplemented castrated mice showed a higher frequency of mortality than castrated males without hormone replacement or nonoperated mice. Analysis of castrated male mice from other strains (A/J, DBA/2J, AKR/J, BALB/cJ) supplemented with 17-β-estradiol presented the opposite effect, a reduction in lipopolysaccharide-induced tumor necrosis factor-α plasma levels. Conclusions: These results suggest that sex steroids can modulate the inflammatory response and the outcome after injury in mice. The effect of sex steroids depends on the genetic background.

Original languageEnglish (US)
Pages (from-to)232-236
Number of pages5
JournalCritical care medicine
Volume31
Issue number1
DOIs
StatePublished - Jan 1 2003

Keywords

  • Gender
  • Injury
  • Lipopolysaccharide
  • Sepsis
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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