title: Impact of burn priming on immune and metabolic functions of whole Liver in a rat cecal ligation and puncture model.
abstract: Previously, we have shown that systemic insults in single injury models produced immunosuppressive effects in burn, and a strong acute phase response in sepsis through hepatic gene expression. In order to investigate the implications of these effects on a combined injury, a double hit model was explored to mimic the progression of clinical burn-sepsis. Rodents were subjected to a 20% total body surface area (TSA) full-thickness burn injury, and 48 hours later underwent cecal ligation and puncture (CLP) to induce sepsis. Pathways related to innate immune signaling through cytokines and NF-KB were co regulated with xenobiotic metabolism genes and acute phase protein genes, and that these genes were suppressed early, and then activated. Furthermore, we were able to identify that, in addition to amino acid metabolism, pyruvate metabolism, fatty acid metabolism and NRF-2 mediated oxidative stress genes were down regulated over the time course. Overall, these observed trends within the double hit burn-sepsis model represent unique immune and metabolic pathways and dynamics not found in either injury, including an early suppression followed by overreaction of pro inflammatory mediators, and an increase in amino acid metabolism at the expense of central carbon pathways.
authors: Chemical and Biochemical Engineering Department, Rutgers, the State University of New Jersey Piscataway, NJ, 08854, USA.
authors: John Sa
authors: JS
authors: Mattick
authors: Qian
authors: Q
authors: Yang
authors: Mehmet A
authors: MA
authors: Orman
authors: Marianthi G
authors: MG
authors: Ierapetritou
authors: Francois
authors: F
authors: Berthiaume
authors: Stephen C
authors: SC
authors: Gale
authors: Ioannis P
authors: IP
authors: Androulakis
keywords: RT-PCR analysis; Sepsis; burns; liver; microarray analysis
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