Cytokine expression profile over time in severely burned pediatric patients.
ABSTRACT A severe burn leads to hypermetabolism and catabolism resulting in compromised function and structure of essential organs. The massive release of cytokines is implicated in this hypermetabolic response. The aim of the present study was to compare cytokine expression profiles from severely burned children without signs of infections or inhalation injury (n = 19) to the cytokine profiles from normal, noninfected, nonburned children (n = 14). The Bio-Plex suspension array system was used to measure the concentration of 17 cytokines. The expression of proinflammatory and anti-inflammatory cytokines was maximal during the first week after thermal injury. Significant increases were measured for 15 mediators during the first week after thermal injury: interleukin (IL) 1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 p70, IL-13, IL-17, interferon gamma, monocyte chemoattractant protein 1, macrophage inflammatory protein 1beta, and granulocyte colony-stimulating factor (P < 0.05). Granulocyte-macrophage colony-stimulating factor was significantly increased during the second week after burn (P < 0.05). Within 5 weeks, the serum concentrations of most cytokines decreased, approaching normal levels. When compared with the cytokine levels measured in normal children, a total of 16 cytokines were significantly altered (P < 0.05). After severe burn, a specific cytokine expression profile is observed in patients without complications such as inhalation injury or sepsis. The cytokine concentrations decrease during 5 weeks after burn but remain elevated over nonburned values. Furthermore, the elevation in most serum cytokine levels during the first week after burn may indicate a potential window of opportunity for therapeutic intervention.
- SourceAvailable from: Hans Christoph Pape[Show abstract] [Hide abstract]
ABSTRACT: The interaction between the complex pattern of cytokine release and remote organ dysfunction after trauma is incompletely understood. The aim of this study was to investigate the pattern of cytokine release and its association with the evolution of remote organ dysfunction after bilateral femur fracture. Male C57/BL6 mice were euthanized at six different time points (1-6 h) after bilateral femur fracture. Serum cytokine concentrations were measured with the Luminex multiplexing platform, and serum alanine aminotransferase levels were measured with the Vitros 950 Chemistry System. Hepatic and pulmonary myeloperoxidase activity was determined with an enzyme-linked immunosorbent assay kit. Permeability changes of the lung were assessed via bronchoalveolar lavage, and those of the liver via assessment of edema formation. Serum TNF-alpha was unchanged in the fracture group throughout the experiment. Serum IL-6 and keratinocyte levels peaked at 5 h postinjury, whereas IL-10 levels peaked at 2 and 6 h. A brief IL-1beta peak was observed at 3 h after fracture. Hepatic and pulmonary myeloperoxidase activity was significantly elevated within 1 h after trauma. Hepatic permeability was significantly increased within 2 h, and pulmonary permeability was significantly increased within 6 h after injury. Serum alanine aminotransferase levels peaked at 3 and 5 h postinjury. The pattern of serum IL-6, keratinocyte, IL-10, and IL-1beta release was dynamic, whereas no significant elevations in TNF-alpha were observed. The early hepatic and pulmonary infiltration of polymorphonuclear cells occurred in the absence of significantly elevated serum cytokine levels, suggesting that either early minor changes with an unbalance in inflammatory mediators or locally produced cytokines may initiate this process.Shock 08/2008; 30(1):43-7. · 2.61 Impact Factor
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ABSTRACT: BACKGROUND: When urgently intubating patient in the burn intensive care unit (BICU), various induction agents, including propofol, are utilized that may induce hemodynamic instability. METHODS: A retrospective review was performed of consecutive critically ill burn patients who underwent urgent endotracheal intubation in BICU. Basic burn-related demographic data, indication for intubation, and induction agents utilized were recorded. The primary outcomes of interest were clinically significant hypotension requiring immediate fluid resuscitation, initiation or escalation of vasopressors immediately after intubation. Secondary outcomes included ventilator days, stay length, and in-hospital mortality. RESULTS: Between January 2003 and August 2010, we identified 279 urgent intubations in 204 patients. Of these, the criteria for presumed sepsis were met in 60% (n=168) of the intubations. After intubation, 117 patients (42%) experienced clinically significant hypotension. Propofol (51%) was the most commonly utilized induction agent followed by etomidate (23%), ketamine (15%), and midazolam (11%). On multiple logistic regression, %TBSA (OR 1.016, 95% CI 1.004-1.027, p<0.001) and presumed sepsis (OR 1.852, 95% CI 1.100-3.117, p=0.02) were the only significant predictors of hypotension. None of the induction agents, including propofol, were significantly associated with hypotension in patients with or without presumed sepsis. CONCLUSIONS: In critically ill burn patients undergoing urgent endotracheal intubation, specific induction agents, including propofol, were not associated with clinically significant hypotension. Presumed sepsis and %TBSA were the most important risk factors.Burns: journal of the International Society for Burn Injuries 08/2012; · 1.95 Impact Factor
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ABSTRACT: Severe burn induces rapid skeletal muscle proteolysis after the injury, which persists for up to 1 year and results in skeletal muscle atrophy despite dietary and rehabilitative interventions. The purpose of this research was to determine acute changes in gene expression of skeletal muscle mass regulators postburn injury. Specimens were obtained for biopsy from the vastus lateralis of a nonburned leg of eight burned subjects (6M, 2F: 34.8 ± 2.7 years: 29.9 ± 3.1% TBSA burn) at 5.1 ± 1.1 days postburn injury and from matched controls. mRNA expression of cytokines and receptors in the tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) families, and the ubiquitin proteasome E3 ligases, atrogin-1 and MuRF-1, was determined. TNF receptor 1A was over 3.5-fold higher in burn. Expression of TNF-like weak inducer of apoptosis and its receptor were over 1.6 and 6.0-fold higher in burn. IL-6, IL-6 receptor, and glycoprotein 130 were elevated in burned subjects with IL-6 receptor over 13-fold higher. The level of suppressor of cytokine signaling-3 was also increased nearly 6-fold in burn. Atrogin-1 and MuRF-1 were more than 4- and 3-fold higher in burn. These results demonstrate for the first time that severe burn in humans has a remarkable impact on gene expression in skeletal muscle of a nonburned limb of genes that promote inflammation and proteolysis. Because these changes likely contribute to the acute skeletal muscle atrophy in areas not directly affected by the burn, in the future it will be important to determine the responsible systemic cues.Journal of burn care & research: official publication of the American Burn Association 06/2013; · 1.54 Impact Factor