SPP 1151:  Immune and Metabolic Modulation Induced by Severe Tissue Trauma

• Subject Area: Medicine
• Term: from 2003 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5471904

Trauma-derived diseases are among the top ranking illnesses with regard to clinical and economical importance. Immunological and metabolic consequences of severe trauma seem to constitute major determinators of possible clinical complications. This Priority Programme is focussed on the molecular basis of the underlying events:-- Analysis of the factors being produced by local tissue destruction, in particular by ischemia and reperfusion caused through injury. Besides radicals derived from oxide and nitric oxide these may be represented by danger signals for the immune system e.g. heat shock proteins. Such signals might be primary driving forces for the generalized inflammation caused by trauma in the absence of microbial stimuli. In this context, "hypoxia-induced-factor I" might be of key importance since it coordinates hypoxic tissue responses. Although much argues for a functional involvement of the above factors in the consequences of tissue destruction, little evidence exists on their factual role in clinical trauma.-- Analysis of genetic constellations ("single nucleotide polymorphisms") disposing for adverse reactions following trauma and differential gene expression induced by trauma. Such studies allow the determination of factors potentially involved in the posttraumatic development (SIRS and CARS). Within the framework of the Priority Programme we have the opportunity to study these items in a great number of patients. This project also embraces clinics not directly included in the Priority Programme contributing patient´s material. -- Injury of certain regions such as brain injuries or lung contusion are known to pave the way for multi-organ failure or bacterial infections. It is far from being clear which organ specific particularities account for this. A more profound knowledge of the signals originating from the organs in question seems to be necessary for the development of clinical strategies with regard to posttraumatic multi-organ failure.

• DFG Programme: Priority Programmes
• International Connection: Switzerland, USA

Projects

• Activation mechanisms by TREM-1 and it´s significance in immunomodulation post trauma (Applicant Radsak, Markus P. )
• Biometrical support for the priority program "Immune and Metabolic Modulation induced by severe Tissue Trauma" and data mining approaches for the identification of disease associated single nucleotide polymorphismus (SNPs) (Applicant Koenig, Inke Regina )
• Coordinator´s fund (Applicant Schade, Fritz Ulrich )
• Free radicals in mechanical trauma to the muscle. Identification of the contributing species, mechanisms of their formation, and their effects on metabolic and immunologic functions (Applicant de Groot, Herbert )
• Genetic pathogenesis of tissue injury-induced apoptosis of immunocompetent and parenchymal cells (Applicant Ertel, Wolfgang )
• Genetic Predisposition for Adverse Outcomes in Trauma Patients (Applicant Stüber, Frank )
• Genetic predisposition to pathologic inflammation in trauma patients with respect to the ISS based on data from cooperating centers (Applicant Jöckel, Karl-Heinz )
• Infiltration, migration and function of leukocytes in trauma-induced immunomodulation and the involvement of Heat-Shock Proteins (Applicant Flohé, Stefanie )
• Influence of beta-Defensin-2, -3 und -4 gene copy number variations on gene transcription and protein expression, and their impact on infectious complications in trauma patients (Applicant Book, Malte )
• Interactions between local and systemic immune response following controlled cortical impact injury in a rat model (Applicant Thomale, Ulrich )
• Local and systemic activation of caspase-1 dependent interleukins and matrix-metalloproteinases in developmental brain trauma (Applicant Ikonomidou, Hrissanthi )
• Mechanism of activation of blood monocytes following major trauma (Applicant Jack, Robert S. )
• Mechanisms and meaning of activation of Hypoxia-Inducible-Factor-1 (HIF-1) in muscle after mechanical trauma (Applicant Fandrey, Joachim )
• Multiparametric functional analysis of monocytic and lymphocytic subpopulations after severe multiple injury (Applicant Faist, Eugen )
• Neuroinflammation and neuronal apoptosis in experimental closed head injury in mice (Applicant Ertel, Wolfgang )
• Physiologic role of ubiquitin after severe tissue trauma (Applicant Majetschak, Matthias )
• The Role of Apoptosis in Alveolar Type II and Pulmonary Microvascular Endothelial Cells in the Inflammatory Response After Blunt Chest Trauma (Applicant Knöferl, Markus W. )

• Spokesperson: Professor Dr. Fritz Ulrich Schade