Long-term dynamic profiling of inflammatory mediators in double-hit burn and sepsis animal models

Abstract

Burn injuries together with its subsequent complications, mainly bacterial infections originating from gastrointestinal tract, activate the host immune system through stimulation of a series of local and systemic responses, including the release of inflammatory mediators. To gain a more comprehensive understanding of these complex physiological changes and to propose therapeutic approaches to combat the deleterious consequences of burn and septic shocks, it is essential to analyze animal models of burn and sepsis. In this study, we analyzed the long term profiles of cytokines and chemokines in rat models which received burn injury followed two days later by cecal ligation and puncture (CLP) to induce sepsis and were sacrificed at different time points within 10 days (0, 1, 2, 3, 4, 7 and 10 days). It was observed that MCP-1 concentrations were elevated in all animal models following the burn injury or CLP treatment. IP-10 concentration was persistently decreased after CLP or sham-CLP treatments. GRO/KC concentration was also increased following the burn injury and CLP. It was elucidated that, in more severe injury model which received both burn and CLP treatments, GMCSF and MIP-1α (chemokines), IL-1α (a pro-inflammatory cytokine) and IL-6 (exhibiting both pro- and anti-inflammatory behaviors) were upregulated on the 7th and 10th days, which might be to protect the host system from the subsequent complications caused by burn and sepsis. In order to elucidate critical regulatory interactions, putative transcription factors of the inflammatory mediators which have been significantly changed following the injuries were further identified by analyzing the conserved regions of the promoters of cytokines and chemokines. In conclusion, the long term profiles of the inflammatory mediators were profoundly characterized in this study to gain a comprehensive understanding of inflammatory mediators’ behaviors in various injury models.

Dynamics of hepatic gene expression and serum cytokine profiles in single and double-hit burn and sepsis animal models

“…In this article, we present both the hepatic gene expression and circulating cytokine/chemokine protein expression data for the above-mentioned experimental model to gain insights into the temporal dynamics of the inflammatory and hypermetabolic response following burn and septic injury. This data article supports results discussed in research articles (Yang et al, 2012 [1,4] ; Mattick et al 2012, 2013 [2,3] ; Nguyen et al, 2014 [5] ; Orman et al, 2011, 2012 [6–8] ).…”

“…Further information regarding the array is available at the manufacturer׳s website ( http://www.affymetrix.com ) [1–5] . Temporal variation in serum concentrations of a panel of 23 serum cytokines and chemokines is analyzed at the protein (peptide) level [6–8] . The selected panel includes both pro-inflammatory and anti-inflammatory cytokines and chemokines whose expression is commonly altered after burn injury and sepsis.…”

“… The effect of burn priming on metabolic and immune gene expression in the rat liver is determined in the animal model of sepsis [3] . The dynamics of the early and long-term response in serum cytokine profiles is determined in the single-hit burn model and the single-hit sepsis model as well as in the double-hit burn and sepsis model [7,6,8] . The data can be used to identify patterns of circadian gene expression in the homeostatic rat liver [5] .…”

Thermal Injury Lowers the Threshold for Radiation-Induced Neuroinflammation and Cognitive Dysfunction

“…Importantly, many of these studies were carried out in males (17, 32, 36, 41). We used female mice in our experiments and it has been shown that female mice have a less severe response after burn injury compared to males (40). This suggests that the changes we observed could be under representative of the population as a whole.…”

Skeletal muscle atrogene expression and insulin resistance in a rat model of polytrauma

“…The crux of our model is the simultaneous timing of the injuries, which is distinct from “double hit” models, where CLP is performed one or more days after burn injury to model the infection often observed in burn patients (Orman et al. ; Mattick et al. ).…”