Antibiotics improve survival and alter the inflammatory profile in a murine model of sepsis from Pseudomonas aeruginosa pneumonia

Craig M. Coopersmith, Daniel M. Amiot, Paul E. Stromberg, W. Michael Dunne, Christopher G. Davis, Dale F. Osborne, Kareem D. Husain, Isaiah R. Turnbull, Irene E. Karl, Richard S. Hotchkiss, Timothy G. Buchman

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34 Scopus citations

Abstract

Differing antibiotic regimens can influence both survival and the inflammatory state in sepsis. We investigated whether the addition and/or type of antimicrobial agent could effect mortality in a murine model of Pseudomonas aeruginosa pneumonia-induced sepsis and if antibiotics altered systemic levels of cytokines. FVB/N mice were subjected to intratracheal injection of pathogenic bacteria and were given gentamicin, imipenem, or 0.9% NaCl 2 h after surgery, which continued every 12 h for a total of six doses. Survival at 7 days (n = 24 in each group) was 100% for mice given gentamicin, 88% for mice given imipenem, and 8% for sham mice treated with 0.9% NaCl (P < 0.0001). Systemic interleukin (IL) 6 levels were assayed 6 h postoperatively on all mice to see if they were predictive of outcome. Plasma IL-6 levels above 3600 pg/mL were associated with a 100% mortality, levels under 1200 pg/mL were associated with a 100% survival, and levels between 1200 and 3600 pg/mL had no utility in predicting mortality. In a separate experiment, mice were sacrificed at 3, 6, 12 or 24 h after instillation of P. aeruginosa and were assayed for levels of TNF-α, IL-6, IL-10, and IL-12. Significant alterations in the proinflammatory cytokines TNF-α and IL-6 were present at all time points except 3 h between mice treated with antibiotics and sham controls. In contrast, statistically significant differences in the antiinflammatory cytokine IL-10 were present between the groups only at 6 h, and levels of IL-12 were similar at all time points. These results indicate that both gentamicin and imipenem increase survival at least 10-fold in a model of pneumonia-induced monomicrobial sepsis, and this is predominantly associated with a down-regulation of proinflammatory cytokines.

Original languageEnglish
Pages (from-to)408-414
Number of pages7
JournalShock
Volume19
Issue number5
DOIs
StatePublished - May 2003

Keywords

  • Cytokines
  • Gentamicin
  • Imipenem
  • Infection
  • Interleukin 10
  • Interleukin 12
  • Interleukin 6
  • Tumor necrosis factor

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