TY - JOUR
T1 - Antibiotics improve survival and alter the inflammatory profile in a murine model of sepsis from Pseudomonas aeruginosa pneumonia
AU - Coopersmith, Craig M.
AU - Amiot, Daniel M.
AU - Stromberg, Paul E.
AU - Dunne, W. Michael
AU - Davis, Christopher G.
AU - Osborne, Dale F.
AU - Husain, Kareem D.
AU - Turnbull, Isaiah R.
AU - Karl, Irene E.
AU - Hotchkiss, Richard S.
AU - Buchman, Timothy G.
PY - 2003/5
Y1 - 2003/5
N2 - 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.
AB - 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.
KW - Cytokines
KW - Gentamicin
KW - Imipenem
KW - Infection
KW - Interleukin 10
KW - Interleukin 12
KW - Interleukin 6
KW - Tumor necrosis factor
UR - http://www.scopus.com/inward/record.url?scp=4644339849&partnerID=8YFLogxK
U2 - 10.1097/01.shk.0000054370.24363.ee
DO - 10.1097/01.shk.0000054370.24363.ee
M3 - Article
C2 - 12744482
AN - SCOPUS:4644339849
SN - 1073-2322
VL - 19
SP - 408
EP - 414
JO - Shock
JF - Shock
IS - 5
ER -