Prostaglandins as potential biomarkers and therapeutic targets in critical illness-associated immune dysfunction. (360G-Wellcome-099089_Z_12_Z)
The host laboratory has demonstrated that prostaglandin E2 (PGE2) impairs the innate immune systems ability to kill bacteria and that plasma levels are elevated in an immunosuppressive state, cirrhosis. Cirrhosis-induced immune paralysis is fully reversed by PGE2 inhibition. Pilot-data has demonstrated that plasma from patients with community-acquired pneumonia (CAP) induced leukocyte dysfunction increasing in severity between day 1-3, resolving thereafter. This was also reversed with PGE2/D2 an tagonists. Nosocomial infections occur in 5% of hospital and 30% of intensive care admissions annually. I hypothesise that PGE2/D2 underlie critical illness associated immune dysfunction, and aim to identify PGs as prognostic biomarkers and potential therapeutic targets to prevent hospital-acquired secondary infection I will carry out comprehensive lipodomic analysis on plasma of patients admitted to UCLH with a primary diagnosis of CAP. Correlation in temporal changes in eicosanoid levels wi th clinical markers and outcomes will be explored, along with in vitro quantification of PGE2 contribution to immune dysfunction. In parallel, I will use murine cecal-ligation and puncture followed by pneumonia challenge to mechanistically dissect the role of PGs in secondary/opportunistic infection at a receptor, cellular and enzyme level acquiring training in flow assisted cell sorting, animal models of acute/resolving inflammation, pharmacology and molecular biology
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Grant Details
Amount Awarded | 230705 |
Applicant Surname | Fullerton |
Approval Committee | Clinical Interview Committee |
Award Date | 2012-06-27T00:00:00+00:00 |
Financial Year | 2011/12 |
Grant Programme: Title | Research Training Fellowship |
Internal ID | 099089/Z/12/Z |
Lead Applicant | Dr James Fullerton |
Partnership Value | 230705 |
Planned Dates: End Date | 2015-09-30T00:00:00+00:00 |
Planned Dates: Start Date | 2012-10-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |
Sponsor(s) | Prof Derek Gilroy |