title: Differences in the hepatic signal transcription pathway and cytokine expression between thermal injury and sepsis.
abstract: Inflammation and catabolism in response to trauma, surgery, critical illness or bacteria lead to a compromise of essential organs, which can lead to prolonged clinical stay and even death. Mediators responsible for catabolism were thought to be proinflammatory cytokines, but recently the focus has shifted to signal transduction. The purpose of the present study was to determine differences between two pathophysiologic states, sepsis and thermal injury, in signal transduction and cytokine expression and thus define the importance of the signal transcription pathway. Rats were randomly divided to either receive lipopolysaccharide (3 mg/kg body weight or a 30% total body surface area burn) or they received no treatment and served as controls. Animals were sacrificed 1, 2, 5, and 7 days postinsult and serum and liver harvested for analysis. A thermal injury appeared to have a slow release and expression of signal transcription factors and cytokines and a sepsis showed a rapid increase of mediators and also a fast decrease. The changes in cytokine profiles after burn, particularly interleukin-1beta and macrophage inhibitory factor, appear to be mediated by C/EBP-beta and STAT-3, whereas after the induction of a sepsis, tumor necrosis factor and interleukin-6 are mainly mediated by STAT-5. Based on our findings we suggest that the pathophysiologic state of a thermal injury is not comparable with sepsis in association with signal transcription factors and the differences in intracellular and extracellular signaling therefore opens new ideas for therapeutic options.
authors: Klinik und Poliklinik für Chirurgie, Klinikum der Universität Regensburg, Germany.
authors: Dagmar
authors: D
authors: Klein
authors: Ralf
authors: R
authors: Einspanier
authors: Ulrich
authors: U
authors: Bolder
authors: Marc G
authors: MG
authors: Jeschke
mesh_terms: D000818:Animals; D002056:Burns; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006358:Hot Temperature; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D008297:Male; D008894:Milk Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D018805:Sepsis; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D016207:Cytokines; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D008894:Milk Proteins; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators