Prior burn insult induces lethal acute lung injury in endotoxemic mice: Effects of cytokine inhibition

Junichi Sasaki, Seitaro Fujishima, Hiroyuki Iwamura, Korekiyo Wakitani, Sadakazu Aiso, Naoki Aikawa

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Many patients who experience surgical stress, including burn injury, become susceptible to severe sepsis and septic organ dysfunction, which remains the primary contributor to morbidity and mortality in burn patients. In the present study, we developed a murine model of burn-primed sublethal endotoxemia by producing a 15% BSA full-thickness burn on the dorsum of BALB/c mice under ether anesthesia and administering 10 mg/kg of LPS intravenously on day 11 to model endotoxemia. The prior burn injury in this model induced two-peaked production of cytokines, TNF-α, and macrophage inflammatory protein-2 at 2 and 12 h after LPS administration, and it was associated with increased mortality. We also assessed the effect of pharmacological modulation with cytokine synthesis inhibitors prednisolone and JTE-607 and found that pretreatment with them attenuated later cytokine production and decreased mortality after LPS administration. We speculate that the prior burn injury primed the mice for the secondary insult via cytokine production. These results also suggested that an anticytokine strategy might serve as a novel prophylactic therapy for septic organ dysfunction in burn-primed patients.

Original languageEnglish
Pages (from-to)L270-L278
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number2 28-2
Publication statusPublished - 2003 Feb 1


  • Chemokine
  • JTE-607
  • Priming
  • Systemic inflammatory response syndrome
  • Two-hit phenomenon

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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