Mediators in polytrauma--pathophysiological significance and clinical relevance.
Multiple trauma induces an inflammatory response syndrome of the whole body that is triggered by (a) hemorrhage inducing an ischemia/reperfusion (I/R) syndrome and (b) fractures or organ contusions inducing tissue-repair processes. I/R injury generates oxyradical/proteolytic metabolites and adhesion molecules, while tissue and endothelial injury directly stimulate complement, coagulation and kinin pathways. Membrane-derived phospholipase A2 and lipid mediators potentiate cellular interactions and increase microvascular permeability. The tissue-repair process mediates macrophage/monocyte and T-cell activation which releases pro- and anti-inflammatory cytokines. Mediator action follows a "three-level model", proposing that depending on the degree of traumatic injury cellular and humoral responses may spread from a cellular to an organ and then a systemic level. The systemic response can result in a severe immunological dys-homeostasis that potentially hazards the survival of the trauma patient by uncontrollable cellular dysfunction, appearing clinically as multiple organ-dysfunction syndrome. Blood-mediator concentrations often parallel the inflammatory process; initially, high levels of cytokines are followed by severe organ dysfunction. However, interpretation of these data remains difficult due to distinct beneficial or detrimental effects of mediators on the different levels of inflammation and missing prognostic threshold values, indicating a risk of adverse effects. Future studies must determine pro- and anti-inflammatory mediators directly, during the intensive care therapy, and evaluate their clinical relevance prospectively for the different levels of inflammation at local and systemic sites.
Chirurgische Universitätsklinik, Abteilung für Unfall-, Hand- und Wiederherstellungschirurgie, Homburg/Saar, Germany.
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D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D008954:Models, Biological; D009104:Multiple Trauma / Q000503:physiopathology*
D018836:Inflammation Mediators