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Projekt
The impact of MAPK inhibition on lung innate immunity and outcome in a new model of acute trauma/hemorrhage and subsequent pneumococcal pneumonia
Fachliche Zuordnung
Pneumologie,Thoraxchirurgie
Förderung
Förderung von 2007 bis 2010
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 43434755
One key factor in the management of trauma patients suffering from hemorrhagic shock is control of bleeding and rapid fluid resuscitation to improve tissue perfusion. However, despite successful resuscitation, many poly-traumatized patients who survive the initial insult later develop pneumonia progressing into sepsis and multi-organ failure. Severe trauma and hemorrhage triggers a series of events leading to impaired host innate immune responses leaving the organism susceptible to infectious insults. The underlying pathophysiological mechanisms of this immune suppression are poorly understood. It has been recently reported that alterations of important intracellular signaling pathways such as the MAP-kinase and Akt pathway play a critical role for impaired host innate immune functions in experimental models of sepsis and acute inflammation. The aim of this project is to investigate the role of the three major MAPK signaling pathways (p38, ERK1/2, JNK1/2) for the development of impaired lung innate defense mechanisms in a new model of acute trauma/hemorrhage and subsequent pneumonia. Specific inhibitors of the p38, ERK1/2 and JNK1/2 pathways will be administered during experimental trauma/hemorrhage and the effects on lung innate immune functions as well as on outcome during subsequent Streptococcus pneumoniae infection will be studied in detail. The ultimate goal is to develop new therapeutic strategies to limit major immune suppression after acute trauma and hemorrhage in order to specifically prevent subsequent acute pneumonia and sepsis.
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