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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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
Issue number5
StatePublished - May 2003


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


Dive into the research topics of 'Antibiotics improve survival and alter the inflammatory profile in a murine model of sepsis from Pseudomonas aeruginosa pneumonia'. Together they form a unique fingerprint.

Cite this