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.
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ABSTRACT: OBJECTIVES:: Emerging proteomics techniques can be used to establish proteomic outcome signatures and to identify candidate biomarkers for survival following traumatic injury. We applied high-resolution liquid chromatography-mass spectrometry and multiplex cytokine analysis to profile the plasma proteome of survivors and nonsurvivors of massive burn injury to determine the proteomic survival signature following a major burn injury. DESIGN:: Proteomic discovery study. SETTING:: Five burn hospitals across the United States. PATIENTS:: Thirty-two burn patients (16 nonsurvivors and 16 survivors), 19-89 years old, were admitted within 96 hours of injury to the participating hospitals with burns covering more than 20% of the total body surface area and required at least one surgical intervention. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: We found differences in circulating levels of 43 proteins involved in the acute-phase response, hepatic signaling, the complement cascade, inflammation, and insulin resistance. Thirty-two of the proteins identified were not previously known to play a role in the response to burn. Interleukin-4, interleukin-8, granulocyte macrophage colony-stimulating factor, monocyte chemotactic protein-1, and β2-microglobulin correlated well with survival and may serve as clinical biomarkers. CONCLUSIONS:: These results demonstrate the utility of these techniques for establishing proteomic survival signatures and for use as a discovery tool to identify candidate biomarkers for survival. This is the first clinical application of a high-throughput, large-scale liquid chromatography-mass spectrometry-based quantitative plasma proteomic approach for biomarker discovery for the prediction of patient outcome following burn, trauma, or critical illness.Critical care medicine 03/2013; · 6.37 Impact Factor
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ABSTRACT: Severe burns induce a pathophysiological response that affects almost every physiological system within the body. Inflammation, hypermetabolism, muscle wasting, and insulin resistance are all hallmarks of the pathophysiological response to severe burns, with perturbations in metabolism known to persist for several years post injury. Skeletal muscle is the principal depot of lean tissue within the body and as the primary site of peripheral glucose disposal, plays an important role in metabolic regulation. Following a large burn, skeletal muscle functions as and endogenous amino acid store, providing substrates for more pressing functions, such as the synthesis of acute phase proteins and the deposition of new skin. Subsequently, burn patients become cachectic, which is associated with poor outcomes in terms of metabolic health and functional capacity. While a loss of skeletal muscle contractile proteins per se will no doubt negatively impact functional capacity, detriments in skeletal muscle quality, i.e. a loss in mitochondrial number and/or function may be quantitatively just as important. The goal of this review article is to summarise the current understanding of the impact of thermal trauma on skeletal muscle mitochondrial content and function, to offer direction for future research concerning skeletal muscle mitochondrial function in patients with severe burns, and to renew interest in the role of these organelles in metabolic dysfunction following severe burns.Burns: journal of the International Society for Burn Injuries 05/2013; · 1.95 Impact Factor
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ABSTRACT: Time-course high-throughput gene expression data are emerging in genomic and translational medicine. Extracting interesting time-course patterns from a patient cohort can provide biological insights for further clinical research and patient treatment. We propose principal trend analysis (PTA) to extract principal trends of time-course gene expression data from a group of patients, and identify genes that make dominant contributions to the principal trends. Through simulations, we demonstrate the utility of PTA for dimension reduction, time-course signal recovery and feature selection with high-dimensional data. Moreover, PTA derives new insights in real biological and clinical research. We demonstrate the usefulness of PTA by applying it to longitudinal gene expression data of a circadian regulation system and burn patients. These applications show that PTA can extract interesting time-course trends with biological significance, which helps the understanding of biological mechanisms of circadian regulation systems as well as the recovery of burn patients. Overall, the proposed PTA approach will benefit the genomic medicine research. Our method is implemented into an R-package: PTA (Principal Trend Analysis).01/2014;