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Prior burn insult induces lethal acute lung injury in endotoxemic mice: effects of cytokine inhibition
- Source :
- The American Journal of Physiology. Feb, 2003, Vol. 284 Issue 2, pL270, 9 p.
- Publication Year :
- 2003
-
Abstract
- 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-[alpha], 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. two-hit phenomenon; priming; systemic inflammatory response syndrome; chemokine; JTE-607
- Subjects :
- Lungs -- Injuries
Burns and scalds -- Research
Burns and scalds -- Physiological aspects
Burns and scalds -- Care and treatment
Fires -- Physiological aspects
Cytokines -- Physiological aspects
Prednisolone -- Usage
Inflammation -- Physiological aspects
Mice -- Usage
Mice -- Physiological aspects
Bacterial infections -- Physiological aspects
Bacterial infections -- Prevention
Biological sciences
Subjects
Details
- ISSN :
- 00029513
- Volume :
- 284
- Issue :
- 2
- Database :
- Gale General OneFile
- Journal :
- The American Journal of Physiology
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.98641718