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WHY DO THEY DIE? DECIPHERING AND QUELLING THE LETHAL CUES OF IMMUNO-INFLAMMATORY RESPONSE IN SEPSIS

Objective

Sepsis is a multifaceted disease that remains a serious clinical problem and causes frequent mortality in human patients worldwide. The proposed project addresses the mechanisms and prevention of early mortality in experimental sepsis. To replicate human sepsis, murine models of live Escherichia coli and Streptococcus pyogenes systemic infusion and cecal ligation and puncture (CLP) peritonitis will be used. The project consists of three aims investigating acute immuno-inflammatory signaling triggered by a septic event: Aim I will study the role and modulation of differential genomic expression upon survival/mortality in gram-negative vs. gram-positive systemic sepsis. Based on the retrospective comparison of outcome in CLP sepsis, Aim II will differentiate between the non-lethal and lethal: (1)-gene/protein expression of inflammatory cytokines and (2)-changes in neurotransmitter fluctuations in different brain regions. Aim III will employ the novel strategy of prospective outcome-based stratification and investigate the effectiveness/mechanism of immuno-modulative anti-inflammatory therapy upon survival in mice predicted to die of acute CLP-induced polymicrobial peritonitis. There is an urgent need for treatments improving outcomes in sepsis and a rise of a new effective, individual patient-based therapy against sepsis is contingent upon exhaustive understanding of its immuno-inflammatory fingerprints. Successful accomplishment of the projected study will contribute to this effort.

Field of science

  • /social sciences/sociology/demography/mortality

Call for proposal

FP7-PEOPLE-2007-4-3-IRG
See other projects for this call

Funding Scheme

MC-IRG - International Re-integration Grants (IRG)

Coordinator

LUDWIG BOLTZMANN GESELLSCHAFT OSTERREICHISCHE VEREINIGUNG ZUR FORDERUNG DER WISSENSCHAFTLICHEN FORSCHUNG
Address
Nussdorfer Strasse 64/6
1090 Wien
Austria
Activity type
Research Organisations
EU contribution
€ 100 000
Administrative Contact
Soheyl Bahrami (Prof.)